Potential molecular targets for intervention in pelvic organ prolapse

Wu, Xia; Liu, Xiaochun; Li, Tingting

doi:10.3389/fmed.2023.1158907

Title: Potential molecular targets for intervention in pelvic organ prolapse

Journal Article · 05 September 2023 · Frontiers in Medicine

DOI: https://doi.org/10.3389/fmed.2023.1158907 · OSTI ID:1998206

Wu, Xia; Liu, Xiaochun; Li, Tingting

Pelvic organ prolapse (POP) is a concerning gynecological benign illness in middle-aged and senior women. Its etiology is complex, the incidence rate is high, symptoms are clinically subjective, and its influence tends to be polarized. At present, for those who need medical treatment, whether surgical or non-surgical, complications cannot be ignored, and treatment effect needs to be optimized. However, there is a lack of accurate molecular biological interventions for the prevention, diagnosis, progression delay, and treatment of POP. Here, we reviewed the current state of understanding of the molecular mechanisms and factors associated with POP etiology. These factors include cyclins, matrix metal peptidases/tissue inhibitors of metalloproteinases, microRNAs, homeobox A11, transforming growth factor β1, insulin-like growth factor 1, fibulin 5, lysyl oxidase-like 1, oxidative stress, inflammatory response, estrogen, and other potential biomarkers associated with POP. In addition, relevant molecular targets that may be used to intervene in POP are summarized. The aim of this review was to provide more information to identify accurate potential biomarkers and/or molecular targets for the prevention, diagnosis, progression delay, and treatment of POP, with the goal of improving medical treatment for patients at-risk for POP or having POP. Continued research is needed to identify additional details of currently accepted molecular mechanisms and to identify additional mechanisms that contribute to POP.

View Journal Article

Cite

Export

Save

Sponsoring Organization:: USDOE Office of Electricity (OE), Advanced Grid Research & Development. Power Systems Engineering Research

OSTI ID:: 1998206

Journal Information:: Frontiers in Medicine, Journal Name: Frontiers in Medicine Vol. 10; ISSN 2296-858X

Publisher:: Frontiers Media SACopyright Statement

Country of Publication:: Switzerland

Language:: English

References (115)

In Vivo Stimulation of De Novo Collagen Production Caused by Cross-linked Hyaluronic Acid Dermal Filler Injections in Photodamaged Human Skin Wang, Frank; Garza, Luis A.; Kang, Sewon Archives of Dermatology, Vol. 143, Issue 2 https://doi.org/10.1001/archderm.143.2.155	journal	February 2007
An overview of microRNAs: Biology, functions, therapeutics, and analysis methods Saliminejad, Kioomars; Khorram Khorshid, Hamid Reza; Soleymani Fard, Shahrzad Journal of Cellular Physiology, Vol. 234, Issue 5 https://doi.org/10.1002/jcp.27486	journal	November 2018
Proteomics of Uterosacral Ligament Connective Tissue from Women with and without Pelvic Organ Prolapse Li, Xiang‐Juan; Pan, Hai‐Tao; Chen, Juan‐Juan PROTEOMICS – Clinical Applications, Vol. 13, Issue 4 https://doi.org/10.1002/prca.201800086	journal	December 2018
Decrease in p53 Protein in Cultured Cardinal Ligament Fibroblasts from Patients with Prolapsus Uteri Yamamoto, M. Cell Biology International, Vol. 22, Issue 1 https://doi.org/10.1006/cbir.1997.0207	journal	January 1998
Increased expression of matrix metalloproteinase 2 in uterosacral ligaments is associated with pelvic organ prolapse Gabriel, Boris; Watermann, Dirk; Hancke, Katharina International Urogynecology Journal, Vol. 17, Issue 5 https://doi.org/10.1007/s00192-005-0045-y	journal	December 2005
Roles of estrogen receptor, progesterone receptor, p53 and p21 in pathogenesis of pelvic organ prolapse Bai, Sang Wook; Chung, Da Jung; Yoon, Jung Mi International Urogynecology Journal, Vol. 16, Issue 6 https://doi.org/10.1007/s00192-005-1310-9	journal	May 2005
LOXL1 deficiency negatively impacts the biomechanical properties of the mouse vagina and supportive tissues Alperin, Marianna; Debes, Kristen; Abramowitch, Steven International Urogynecology Journal, Vol. 19, Issue 7 https://doi.org/10.1007/s00192-008-0561-7	journal	February 2008
Estrogen receptor alpha polymorphism is associated with pelvic organ prolapse risk Chen, Huey-Yi; Chung, Ya-Wen; Lin, Wei-Yong International Urogynecology Journal, Vol. 19, Issue 8 https://doi.org/10.1007/s00192-008-0603-1	journal	April 2008
Fibulin-5 expression is decreased in women with anterior vaginal wall prolapse Takacs, Peter; Nassiri, Mehdi; Viciana, Anita International Urogynecology Journal, Vol. 20, Issue 2 https://doi.org/10.1007/s00192-008-0757-x	journal	November 2008
Does COLIA1 SP1-binding site polymorphism predispose women to pelvic organ prolapse? Feiner, Benjamin; Fares, Fuad; Azam, Nail International Urogynecology Journal, Vol. 20, Issue 9 https://doi.org/10.1007/s00192-009-0895-9	journal	May 2009
LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse Alarab, May; Bortolini, Maria AT; Drutz, Harold International Urogynecology Journal, Vol. 21, Issue 11 https://doi.org/10.1007/s00192-010-1199-9	journal	June 2010
The polymorphisms of the MMP-1 and the MMP-3 genes and the risk of pelvic organ prolapse Skorupski, Paweł; Jankiewicz, Katarzyna; Miotła, Paweł International Urogynecology Journal, Vol. 24, Issue 6 https://doi.org/10.1007/s00192-012-1970-1	journal	October 2012
Epidemiology and outcome assessment of pelvic organ prolapse Barber, Matthew D.; Maher, Christopher International Urogynecology Journal, Vol. 24, Issue 11 https://doi.org/10.1007/s00192-013-2169-9	journal	October 2013
Identification of pelvic organ prolapse risk susceptibility gene SNP locus in Xinjiang women Abulaizi, Aibibuhan·; Abula, Abudoureyimu·; Ababaikeli, Gulina· International Urogynecology Journal, Vol. 31, Issue 1 https://doi.org/10.1007/s00192-019-04039-z	journal	July 2019
Upregulation of PTK7 and β-catenin after vaginal mechanical dilatation: an examination of fibulin-5 knockout mice Uemura, Ryo; Tachibana, Daisuke; Shiota, Masayuki International Urogynecology Journal, Vol. 32, Issue 11 https://doi.org/10.1007/s00192-021-04693-2	journal	February 2021
Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse Allen-Brady, Kristina; Chua, John W. F.; Cuffolo, Romana International Urogynecology Journal, Vol. 33, Issue 1 https://doi.org/10.1007/s00192-021-04782-2	journal	April 2021
Type I collagen and matrix metalloproteinase 1, 3 and 9 gene polymorphisms in the predisposition to pelvic organ prolapse Ferrari, Maria Maddalena; Rossi, Gabriela; Biondi, Maria Luisa Archives of Gynecology and Obstetrics, Vol. 285, Issue 6 https://doi.org/10.1007/s00404-011-2199-9	journal	December 2011
Expression of COX-2 and Nrf2/GPx3 in the anterior vaginal wall tissues of women with pelvic organ prolapse Lin, Te; Ji, Yuting; Zhao, Ying Archives of Gynecology and Obstetrics, Vol. 303, Issue 5 https://doi.org/10.1007/s00404-020-05913-8	journal	January 2021
Sequence variant in the laminin γ1 (LAMC1) gene associated with familial pelvic organ prolapse Nikolova, Ganka; Lee, Hane; Berkovitz, Suzanne Human Genetics, Vol. 120, Issue 6 https://doi.org/10.1007/s00439-006-0267-1	journal	October 2006
Quantitative Morphometry of Elastic Fibers in Pelvic Organ Prolapse Dahal, Shataakshi; Kuang, Mei; Rietsch, Anna Annals of Biomedical Engineering, Vol. 49, Issue 8 https://doi.org/10.1007/s10439-021-02760-9	journal	March 2021
Changes in biological characteristics during the cellular aging of ligament fibroblasts derived from patients with prolapsus uteri Yamamoto, Mari; Akazawa, Kenji; Aoyagi, Masaru Mechanisms of Ageing and Development, Vol. 115, Issue 3 https://doi.org/10.1016/S0047-6374(00)00121-4	journal	June 2000
Estrogen increases collagen I and III mRNA expression in the pelvic support tissues of the rhesus macaque Clark, Amanda L.; Slayden, Ov D.; Hettrich, Kevin American Journal of Obstetrics and Gynecology, Vol. 192, Issue 5 https://doi.org/10.1016/j.ajog.2004.11.042	journal	May 2005
Biomechanical properties of the vaginal wall: effect of pregnancy, elastic fiber deficiency, and pelvic organ prolapse Rahn, David D.; Ruff, Matthew D.; Brown, Spencer A. American Journal of Obstetrics and Gynecology, Vol. 198, Issue 5 https://doi.org/10.1016/j.ajog.2008.02.022	journal	May 2008
Predicting the number of women who will undergo incontinence and prolapse surgery, 2010 to 2050 Wu, Jennifer M.; Kawasaki, Amie; Hundley, Andrew F. American Journal of Obstetrics and Gynecology, Vol. 205, Issue 3 https://doi.org/10.1016/j.ajog.2011.03.046	journal	September 2011
Genetic epidemiology of pelvic organ prolapse: a systematic review Ward, Renée M.; Velez Edwards, Digna R.; Edwards, Todd American Journal of Obstetrics and Gynecology, Vol. 211, Issue 4 https://doi.org/10.1016/j.ajog.2014.04.006	journal	October 2014
Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women Cartwright, Rufus; Kirby, Anna C.; Tikkinen, Kari A. O. American Journal of Obstetrics and Gynecology, Vol. 212, Issue 2 https://doi.org/10.1016/j.ajog.2014.08.005	journal	February 2015
Crosstalk between calpain activation and TGF-β1 augments collagen-I synthesis in pulmonary fibrosis Li, Feng-Zhi; Cai, Peng-Cheng; Song, Lin-Jie Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol. 1852, Issue 9 https://doi.org/10.1016/j.bbadis.2015.06.008	journal	September 2015
Estrogen receptor beta gene haplotype is associated with pelvic organ prolapse Chen, Huey-Yi; Wan, Lei; Chung, Ya-Wen European Journal of Obstetrics & Gynecology and Reproductive Biology, Vol. 138, Issue 1 https://doi.org/10.1016/j.ejogrb.2007.12.013	journal	May 2008
Changes in expression of fibulin-5 and lysyl oxidase-like 1 associated with pelvic organ prolapse Jung, Hyun Joo; Jeon, Myung Jae; Yim, Ga Won European Journal of Obstetrics & Gynecology and Reproductive Biology, Vol. 145, Issue 1 https://doi.org/10.1016/j.ejogrb.2009.03.026	journal	July 2009
Matrix metalloproteinase-9 polymorphism and risk of pelvic organ prolapse in Taiwanese women Chen, Huey-Yi; Lin, Wei-Yong; Chen, Yung-Hsiang European Journal of Obstetrics & Gynecology and Reproductive Biology, Vol. 149, Issue 2 https://doi.org/10.1016/j.ejogrb.2009.12.014	journal	April 2010
Difference in expression of collagen type I and matrix metalloproteinase-1 in uterosacral ligaments of women with and without pelvic organ prolapse Vulic, Marko; Strinic, Tomislav; Tomic, Snjezana European Journal of Obstetrics & Gynecology and Reproductive Biology, Vol. 155, Issue 2 https://doi.org/10.1016/j.ejogrb.2010.12.019	journal	April 2011
A prospective cohort study of pelvic support changes among nulliparous, multiparous, and pre- and post-menopausal women Sze, Eddie H. M.; Hobbs, Gerry European Journal of Obstetrics & Gynecology and Reproductive Biology, Vol. 160, Issue 2 https://doi.org/10.1016/j.ejogrb.2011.11.016	journal	February 2012
Low expression of collagen type-1 in sacrouterine ligament as risk factor of stage III–IV uterine prolapse Mega Putra, I. Gede; Ngurah Warsita, I. Gusti; Suwiyoga, Ketut European Journal of Obstetrics & Gynecology and Reproductive Biology, Vol. 249 https://doi.org/10.1016/j.ejogrb.2020.01.027	journal	June 2020
The role of transforming growth factor-ß (TGF-ß1) in postmenopausal women with pelvic organ prolapse: An immunohistochemical study Carlin, Greta Lisa; Bodner, Klaus; Kimberger, Oliver European Journal of Obstetrics & Gynecology and Reproductive Biology: X, Vol. 7 https://doi.org/10.1016/j.eurox.2020.100111	journal	July 2020
Nrf2 for protection against oxidant generation and mitochondrial damage in cardiac injury Chen, Qin M. Free Radical Biology and Medicine, Vol. 179 https://doi.org/10.1016/j.freeradbiomed.2021.12.001	journal	February 2022
Quantitative analysis of 17 amino acids in the connective tissue of patients with pelvic organ prolapse using capillary electrophoresis–tandem mass spectrometry Shama, Naz; Bai, Sang Wook; Chung, Bong Chul Journal of Chromatography B, Vol. 865, Issue 1-2 https://doi.org/10.1016/j.jchromb.2008.01.027	journal	April 2008
Metabolomics study of serum and urine samples reveals metabolic pathways and biomarkers associated with pelvic organ prolapse Deng, Wei; Rao, Jun; Chen, Xiaodan Journal of Chromatography B, Vol. 1136 https://doi.org/10.1016/j.jchromb.2019.121882	journal	January 2020
Association between collagen production and mechanical stretching in dermal extracellular matrix: In vivo effect of cross-linked hyaluronic acid filler. A randomised, placebo-controlled study Turlier, Virginie; Delalleau, Alexandre; Casas, Christiane Journal of Dermatological Science, Vol. 69, Issue 3 https://doi.org/10.1016/j.jdermsci.2012.12.006	journal	March 2013
Involvement of Oxidative Stress and Mitochondrial Apoptosis in the Pathogenesis of Pelvic Organ Prolapse Kim, Eun Jae; Chung, Namhyun; Park, Sung Hyo Journal of Urology, Vol. 189, Issue 2 https://doi.org/10.1016/j.juro.2012.09.041	journal	February 2013
Matrix metalloproteinases-1, -2 expression in uterosacral ligaments from women with pelvic organ prolapse Strinic, Tomislav; Vulic, Marko; Tomic, Snjezana Maturitas, Vol. 64, Issue 2 https://doi.org/10.1016/j.maturitas.2009.08.008	journal	October 2009
Fibulin-5 (FBLN5) gene polymorphism is associated with pelvic organ prolapse Khadzhieva, Maryam B.; Kamoeva, Svetlana V.; Chumachenko, Anastasya G. Maturitas, Vol. 78, Issue 4 https://doi.org/10.1016/j.maturitas.2014.05.003	journal	August 2014
Impact of vaginal distention on cell senescence in an animal model of pelvic organ prolapse Hare, Adam M.; Gaddam, Neha G.; Shi, Haolin Tissue and Cell, Vol. 73 https://doi.org/10.1016/j.tice.2021.101652	journal	December 2021
Elastic fiber homeostasis requires lysyl oxidase–like 1 protein Liu, Xiaoqing; Zhao, Yun; Gao, Jiangang Nature Genetics, Vol. 36, Issue 2 https://doi.org/10.1038/ng1297	journal	January 2004
Cell cycle regulation: p53-p21-RB signaling Engeland, Kurt Cell Death & Differentiation, Vol. 29, Issue 5 https://doi.org/10.1038/s41418-022-00988-z	journal	March 2022
Single-cell transcriptome profiling of the vaginal wall in women with severe anterior vaginal prolapse Li, Yaqian; Zhang, Qing-Yang; Sun, Bao-Fa Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-020-20358-y	journal	January 2021
Advancing our understanding of genetic risk factors and potential personalized strategies for pelvic organ prolapse Pujol-Gualdo, Natàlia; Läll, Kristi; Lepamets, Maarja Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-31188-5	journal	June 2022
Targeting oxidative stress in disease: promise and limitations of antioxidant therapy Forman, Henry Jay; Zhang, Hongqiao Nature Reviews Drug Discovery, Vol. 20, Issue 9 https://doi.org/10.1038/s41573-021-00233-1	journal	June 2021
Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank Olafsdottir, Thorhildur; Thorleifsson, Gudmar; Sulem, Patrick Communications Biology, Vol. 3, Issue 1 https://doi.org/10.1038/s42003-020-0857-9	journal	March 2020
Recent updates on the molecular network of elastic fiber formation Shin, Seung Jae; Yanagisawa, Hiromi Essays in Biochemistry, Vol. 63, Issue 3 https://doi.org/10.1042/EBC20180052	journal	August 2019
Decreased endopelvic fascia elastin content in uterine prolapse Klutke, John; Ji, Qing; Campeau, Joseph Acta Obstetricia et Gynecologica Scandinavica, Vol. 87, Issue 1 https://doi.org/10.1080/00016340701819247	journal	January 2008
Progesterone receptor polymorphism is associated with pelvic organ prolapse risk Chen, Huey-Yi; Chung, Ya-Wen; Lin, Wei-Yong Acta Obstetricia et Gynecologica Scandinavica, Vol. 88, Issue 7 https://doi.org/10.1080/00016340902822073	journal	January 2009
Trends in the development of miRNA bioinformatics tools Chen, Liang; Heikkinen, Liisa; Wang, Changliang Briefings in Bioinformatics, Vol. 20, Issue 5 https://doi.org/10.1093/bib/bby054	journal	June 2019
17β-Estradiol suppresses proliferation of fibroblasts derived from cardinal ligaments in patients with or without pelvic organ prolapse Liu, Y. M.; Choy, K. W.; Lui, W. T. Human Reproduction, Vol. 21, Issue 1 https://doi.org/10.1093/humrep/dei296	journal	September 2005
Quantification of Pelvic Organ Prolapse in Mice: Vaginal Protease Activity Precedes Increased MOPQ Scores in Fibulin 5 Knockout Mice1 Wieslander, Cecilia K.; Rahn, David D.; McIntire, Donald D. Biology of Reproduction, Vol. 80, Issue 3 https://doi.org/10.1095/biolreprod.108.072900	journal	March 2009
Knockdown of Hoxa11 In Vivo in the Uterosacral Ligament and Uterus of Mice Results in Altered Collagen and Matrix Metalloproteinase Activity1 Ma, Yan; Guess, Marsha; Datar, Akshita Biology of Reproduction, Vol. 86, Issue 4 https://doi.org/10.1095/biolreprod.111.093245	journal	April 2012
Role of mitofusin 2 (Mfn2) in controlling cellular proliferation Chen, Kuang‐Hueih; Dasgupta, Asish; Ding, Jinhui The FASEB Journal, Vol. 28, Issue 1 https://doi.org/10.1096/fj.13-230037	journal	September 2013
The anatomy of the pelvic floor DeLancey, John O. L. Current Opinion in Obstetrics and Gynecology, Vol. 6, Issue 4 https://doi.org/10.1097/00001703-199408000-00003	journal	August 1994
Pelvic Floor Disorders: The Role of Fascia and Ligaments Norton, Peggy A. Clinical Obstetrics and Gynecology, Vol. 36, Issue 4 https://doi.org/10.1097/00003081-199312000-00017	journal	December 1993
Identification of Six Loci Associated With Pelvic Organ Prolapse Using Genome-Wide Association Analysis Allen-Brady, Kristina; Cannon-Albright, Lisa; Farnham, James M. Obstetrics & Gynecology, Vol. 118, Issue 6 https://doi.org/10.1097/AOG.0b013e318236f4b5	journal	December 2011
Matrix Metalloproteinase-9 Genetic Polymorphisms and the Risk for Advanced Pelvic Organ Prolapse Wu, Jennifer M.; Visco, Anthony G.; Grass, Elizabeth A. Obstetrics & Gynecology, Vol. 120, Issue 3 https://doi.org/10.1097/AOG.0b013e318262234b	journal	September 2012
Pelvic organ prolapse: does hormone therapy use matter? Wasenda, Erika J.; Kamisan Atan, Ixora; Subramaniam, Nishamini Menopause, Vol. 24, Issue 10 https://doi.org/10.1097/GME.0000000000000898	journal	October 2017
Transforming Growth Factor β1 and Extracellular Matrix Protease Expression in the Uterosacral Ligaments of Patients With and Without Pelvic Organ Prolapse Leegant, Ava; Zuckerwise, Lisa C.; Downing, Keith Female Pelvic Medicine & Reconstructive Surgery, Vol. 21, Issue 1 https://doi.org/10.1097/SPV.0000000000000130	journal	January 2015
Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse Couri, Bruna M.; Lenis, Andrew T.; Borazjani, Ali Female Pelvic Medicine & Reconstructive Surgery, Vol. 23, Issue 6 https://doi.org/10.1097/SPV.0000000000000394	journal	January 2017
miR-19-3p Promotes Autophagy and Apoptosis in Pelvic Organ Prolapse Through the AKT/mTOR/p70S6K Pathway: Function of miR-19-3p on Vaginal Fibroblasts by Targeting IGF-1 Yin, Yitong; Qin, Meiying; Luan, Meng Female Pelvic Medicine & Reconstructive Surgery, Vol. 27, Issue 9 https://doi.org/10.1097/SPV.0000000000001034	journal	February 2021
Are Single Nucleotide Polymorphisms Associated With Pelvic Organ Prolapse? Romero, Audrey A.; Jamison, Margaret G.; Weidner, Alison C. Journal of Pelvic Medicine and Surgery, Vol. 14, Issue 1 https://doi.org/10.1097/SPV.0b013e3181637a49	journal	January 2008
Age-related pelvic floor modifications and prolapse risk factors in postmenopausal women Tinelli, Andrea; Malvasi, Antonio; Rahimi, Siavash Menopause, Vol. 17, Issue 1 https://doi.org/10.1097/gme.0b013e3181b0c2ae	journal	January 2010
Does preoperative locally applied estrogen treatment facilitate prolapse‐associated symptoms in postmenopausal women with symptomatic pelvic organ prolapse? A randomised controlled double‐masked, placebo‐controlled, multicentre study Marschalek, M‐L; Bodner, K.; Kimberger, O. BJOG: An International Journal of Obstetrics & Gynaecology, Vol. 128, Issue 13 https://doi.org/10.1111/1471-0528.16894	journal	September 2021
Histopathological evaluation of the uterosacral ligament: is this a dependable structure for pelvic reconstruction? Cole, Emily E.; Leu, Patrick B.; Gomelsky, Alex BJU International, Vol. 97, Issue 2 https://doi.org/10.1111/j.1464-410X.2005.05903.x	journal	February 2006
The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence Jackson, Simon; James, Mark; Abrams, Paul BJOG: An International Journal of Obstetrics and Gynaecology, Vol. 109, Issue 3 https://doi.org/10.1111/j.1471-0528.2002.01052.x	journal	March 2002
High isoprostane level in cardinal ligament-derived fibroblasts and urine sample of women with uterine prolapse Choy, Kw; Liu, Ym; Chu, Cy BJOG: An International Journal of Obstetrics & Gynaecology, Vol. 115, Issue 9 https://doi.org/10.1111/j.1471-0528.2008.01806.x	journal	August 2008
An Integral Theory of Female Urinary Incontinence Petros, Peter E. Papa; Ulmsten, Ulf I. Acta Obstetricia et Gynecologica Scandinavica, Vol. 69, Issue S153 https://doi.org/10.1111/j.1600-0412.1990.tb08027.x	journal	January 1990
Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in humans Hansen, M.; Boesen, A.; Holm, L. Scandinavian Journal of Medicine & Science in Sports https://doi.org/10.1111/j.1600-0838.2011.01431.x	journal	January 2012
Micro RNA ‐30d and micro RNA ‐181a regulate HOXA 11 expression in the uterosacral ligaments and are overexpressed in pelvic organ prolapse Jeon, Myung Jae; Kim, Eun Jae; Lee, Maria Journal of Cellular and Molecular Medicine, Vol. 19, Issue 2 https://doi.org/10.1111/jcmm.12448	journal	January 2015
Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair Kuang, Ping-Ping; Goldstein, Ronald H.; Liu, Yue American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 285, Issue 5 https://doi.org/10.1152/ajplung.00098.2003	journal	November 2003
Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse Rahn, D. D.; Acevedo, J. F.; Word, R. A. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 295, Issue 4 https://doi.org/10.1152/ajpregu.90447.2008	journal	October 2008
Lower urogenital tract anatomical and functional phenotype in lysyl oxidase like-1 knockout mice resembles female pelvic floor dysfunction in humans Lee, Una J.; Gustilo-Ashby, A. Marcus; Daneshgari, Firouz American Journal of Physiology-Renal Physiology, Vol. 295, Issue 2 https://doi.org/10.1152/ajprenal.00063.2008	journal	August 2008
Redox Signaling as a Therapeutic Target to Inhibit Myofibroblast Activation in Degenerative Fibrotic Disease Sampson, Natalie; Berger, Peter; Zenzmaier, Christoph BioMed Research International, Vol. 2014 https://doi.org/10.1155/2014/131737	journal	January 2014
Tissue Composition of the Vaginal Wall in Women with Pelvic Organ Prolapse Meijerink, Aukje M.; van Rijssel, Reinier H.; van der Linden, Paul J. Q. Gynecologic and Obstetric Investigation, Vol. 75, Issue 1 https://doi.org/10.1159/000341709	journal	October 2012
HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse Connell, Kathleen A.; Guess, Marsha K.; Chen, Heidi Journal of Clinical Investigation https://doi.org/10.1172/JCI34193	journal	February 2008
Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans Budatha, Madhusudhan; Roshanravan, Shayzreen; Zheng, Qian Journal of Clinical Investigation, Vol. 121, Issue 5 https://doi.org/10.1172/JCI45636	journal	May 2011
Fibulin-5: two for the price of one maintaining pelvic support Northington, Gina M. Journal of Clinical Investigation, Vol. 121, Issue 5 https://doi.org/10.1172/JCI57438	journal	May 2011
Uterosacral Ligament Smooth Muscle Cell Apoptosis Is Increased in Women With Uterine Prolapse Takacs, Peter; Nassiri, Mehdi; Gualtieri, Marc Reproductive Sciences, Vol. 16, Issue 5 https://doi.org/10.1177/1933719108328611	journal	May 2009
HOXA11 Promotes Fibroblast Proliferation and Regulates p53 in Uterosacral Ligaments Connell, Kathleen A.; Guess, Marsha K.; Chen, Heidi W. Reproductive Sciences, Vol. 16, Issue 7 https://doi.org/10.1177/1933719109334260	journal	July 2009
Gene Expression and Immunoreactivity of Elastolytic Enzymes in the Uterosacral Ligaments From Women With Uterine Prolapse Liang, Ching-Chung; Huang, Hong-Yuan; Chang, Shuenn-Dhy Reproductive Sciences, Vol. 19, Issue 4 https://doi.org/10.1177/1933719111424443	journal	April 2012
Expression of Extracellular Matrix-Remodeling Proteins Is Altered in Vaginal Tissue of Premenopausal Women With Severe Pelvic Organ Prolapse Alarab, May; Kufaishi, Hala; Lye, Stephen Reproductive Sciences, Vol. 21, Issue 6 https://doi.org/10.1177/1933719113512529	journal	June 2014
Common variants in LAMC1 confer risk for pelvic organ prolapse in Chinese population Chen, Juan; Li, Lei; Lang, Jinghe Hereditas, Vol. 157, Issue 1 https://doi.org/10.1186/s41065-020-00140-2	journal	July 2020
Effects of Preoperative Local Estrogen in Postmenopausal Women With Prolapse: A Randomized Trial Rahn, David D.; Good, Meadow M.; Roshanravan, Shayzreen M. The Journal of Clinical Endocrinology & Metabolism, Vol. 99, Issue 10 https://doi.org/10.1210/jc.2014-1216	journal	October 2014
Identiﬁcation of Differentially Expressed Genes in Pelvic Organ Prolapse by RNA-Seq Xie, Ruoyun; Xu, Ying; Fan, Shuixiu Medical Science Monitor, Vol. 22 https://doi.org/10.12659/MSM.900224	journal	November 2016
Transforming Growth Factor Beta 1 and p44/42 Expression in Cardinal Ligament Tissues of Patients with Pelvic Organ Prolapse Zhao, Ying; Xia, Zhijun; Lin, Te Medical Science Monitor, Vol. 27 https://doi.org/10.12659/MSM.930433	journal	March 2021
Immunolocalization of Advanced Glycation End Products, Mitogen Activated Protein Kinases, and Transforming Growth Factor-β/Smads in Pelvic Organ Prolapse Vetuschi, Antonella; Pompili, Simona; Gallone, Anna Journal of Histochemistry & Cytochemistry, Vol. 66, Issue 9 https://doi.org/10.1369/0022155418772798	journal	May 2018
Dysregulation of Protease and Protease Inhibitors in a Mouse Model of Human Pelvic Organ Prolapse Budatha, Madhusudhan; Silva, Simone; Montoya, Teodoro Ignacio PLoS ONE, Vol. 8, Issue 2 https://doi.org/10.1371/journal.pone.0056376	journal	February 2013
IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse Yin, Yitong; Han, Ying; Shi, Chang Open Medicine, Vol. 15, Issue 1 https://doi.org/10.1515/med-2020-0216	journal	September 2020
Structural, functional and molecular pathogenesis of pelvic organ prolapse in patient and Loxl1 deficient mice Li, Yu; Nie, Nanfang; Gong, Lin Aging, Vol. 13, Issue 24 https://doi.org/10.18632/aging.203777	journal	December 2021
Proteins in plasma as a potential biomarkers diagnostic for pelvic organ prolapse Wang, Tao; Liu, Yuqing; Mei, Ling Annals of Translational Medicine, Vol. 9, Issue 14 https://doi.org/10.21037/atm-21-1607	journal	July 2021
Advanced glycation end products (AGEs) downregulate the miR-4429/PTEN axis to promote apoptosis of fibroblasts in pelvic organ prolapse Sima, Yizhen; Li, Lisha; Xiao, Chengzhen Annals of Translational Medicine, Vol. 10, Issue 15 https://doi.org/10.21037/atm-22-628	journal	August 2022
Failure of Elastic Fiber Homeostasis Leads to Pelvic Floor Disorders Liu, Xiaoqing; Zhao, Yun; Pawlyk, Basil The American Journal of Pathology, Vol. 168, Issue 2 https://doi.org/10.2353/ajpath.2006.050399	journal	February 2006
Pelvic Organ Prolapse in Fibulin-5 Knockout Mice Drewes, Peter G.; Yanagisawa, Hiromi; Starcher, Barry The American Journal of Pathology, Vol. 170, Issue 2 https://doi.org/10.2353/ajpath.2007.060662	journal	February 2007
Uterine prolapse: evaluation of glycosaminoglycans in postmenopausal women after estrogen therapy Nunes, J. M. V. Cavalcante; Feldner, P. Cezar; Castro, R. Aquino Climacteric, Vol. 14, Issue 1 https://doi.org/10.3109/13697137.2010.500010	journal	February 2011
Therapeutic Effects of 17β-Estradiol on Pelvic Organ Prolapse by Inhibiting Mfn2 Expression: An In Vitro Study Wang, Xiao-Qing; He, Rui-Ju; Xiao, Bing-Bing Frontiers in Endocrinology, Vol. 11 https://doi.org/10.3389/fendo.2020.586242	journal	November 2020
The protective effect of 17 β-estradiol on human uterosacral ligament fibroblasts from postmenopausal women with pelvic organ prolapse Xie, Ting; Guo, Dan; Guo, Tao Frontiers in Physiology, Vol. 13 https://doi.org/10.3389/fphys.2022.980843	journal	October 2022
Global burden and trends of pelvic organ prolapse associated with aging women: An observational trend study from 1990 to 2019 Wang, Bo; Chen, Yingying; Zhu, Xiaoran Frontiers in Public Health, Vol. 10 https://doi.org/10.3389/fpubh.2022.975829	journal	September 2022
The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis Tzanakakis, George N.; Giatagana, Eirini-Maria; Berdiaki, Aikaterini Cancers, Vol. 13, Issue 10 https://doi.org/10.3390/cancers13102478	journal	May 2021
Mfn2 Ablation in the Adult Mouse Hippocampus and Cortex Causes Neuronal Death Han, Song; Nandy, Priya; Austria, Quillan Cells, Vol. 9, Issue 1 https://doi.org/10.3390/cells9010116	journal	January 2020
Oxidative status of cardinal ligament in pelvic organ prolapse Fang, Gui; Hong, Li; Liu, Cheng Experimental and Therapeutic Medicine https://doi.org/10.3892/etm.2018.6633	journal	August 2018
Role of transforming growth factor β-1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target Liu, Cheng; Wang, Ying; Li, Bing-Shu International Journal of Molecular Medicine, Vol. 40, Issue 2 https://doi.org/10.3892/ijmm.2017.3042	journal	June 2017
Advanced glycation end products decrease collagen I levels in fibroblasts from the vaginal wall of patients with POP via the RAGE, MAPK and NF-κB pathways Chen, Yi-Song; Wang, Xiao-Juan; Feng, Weiwei International Journal of Molecular Medicine, Vol. 40, Issue 4 https://doi.org/10.3892/ijmm.2017.3097	journal	August 2017
Collagen metabolic disorder induced by oxidative stress in human uterosacral ligament-derived fibroblasts: A possible pathophysiological mechanism in pelvic organ prolapse Liu, Cheng; Yang, Qing; Fang, Gui Molecular Medicine Reports, Vol. 13, Issue 4 https://doi.org/10.3892/mmr.2016.4919	journal	February 2016
Role of mechanical strain-activated PI3K/Akt signaling pathway in pelvic organ prolapse Li, Bing-Shu; Guo, Wen-Jun; Hong, Li Molecular Medicine Reports, Vol. 14, Issue 1 https://doi.org/10.3892/mmr.2016.5264	journal	May 2016
Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF-β1 signaling pathway Zhang, Qifan; Liu, Cheng; Hong, Shasha Molecular Medicine Reports, Vol. 15, Issue 1 https://doi.org/10.3892/mmr.2016.5994	journal	December 2016
Mitofusin2 regulates the proliferation and function of fibroblasts: The possible mechanisms underlying pelvic organ prolapse development Wang, Xiaoqing; Wang, Xiaoxiao; Zhou, Yingfang Molecular Medicine Reports https://doi.org/10.3892/mmr.2019.10501	journal	July 2019
Molecular mechanism of extracellular matrix disorder in pelvic organ prolapses Zhang, Liping; Dai, Fangfang; Chen, Gantao Molecular Medicine Reports, Vol. 22, Issue 6 https://doi.org/10.3892/mmr.2020.11564	journal	October 2020
Proteomic Analysis of the Uterosacral Ligament in Postmenopausal Women with and without Pelvic Organ Prolapse Sun, Zhi-Jing; Zhu, Lan; Lang, Jing-He Chinese Medical Journal, Vol. 128, Issue 23 https://doi.org/10.4103/0366-6999.170262	journal	December 2015
Correlations between Mitofusin 2 Expression in Fibroblasts and Pelvic Organ Prolapse Lu, Ye; Chen, Hua-Yun; Wang, Xiao-Qing Chinese Medical Journal, Vol. 130, Issue 24 https://doi.org/10.4103/0366-6999.220307	journal	December 2017
A Non-Invasive Determination of LOXL1 and Fibulin-5 Levels in the Vaginal Secretions of Women with and Without Pelvic Organ Prolapse Garcia, Bobby; Arthur, Afiba; Patel, Bansari Journal of Medical Research and Surgery https://doi.org/10.52916/jmrs214042	journal	April 2021
Expression and significance of lysyl oxidase-like 1 and fibulin-5 in the cardinal ligament tissue of patients with pelvic floor dysfunction Yang, Zhou; Ouyang, Ling; Li, Bo The Journal of Biomedical Research, Vol. 27, Issue 1 https://doi.org/10.7555/JBR.27.20110142	journal	January 2013

Similar Records

Fibulin-5 promotes airway smooth muscle cell proliferation and migration via modulating Hippo-YAP/TAZ pathway

Journal Article · 2017 · Biochemical and Biophysical Research Communications · OSTI ID:22719136

Fu, Jia; Zheng, Mao; Zhang, Xiaofang; +5 more

Cancer and AIDS

Conference · 1985 · OSTI ID:7162232

Vaeth, J M

Quercetin restrains TGF-β1-induced epithelial–mesenchymal transition by inhibiting Twist1 and regulating E-cadherin expression

Journal Article · 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23137257

Feng, Jihong; Song, Dalong; Jiang, SiYuan; +6 more

Title: Potential molecular targets for intervention in pelvic organ prolapse

Citation Formats

References (115)

Similar Records

Related Subjects