Inhibition of Pin1 alleviates myocardial fibrosis and dysfunction in STZ-induced diabetic mice

Liu, Xue; Liang, Ershun; Song, Xiuhui; Du, Zhanhui; Zhang, Yun; Zhao, Yuxia

doi:10.1016/J.BBRC.2016.09.050

Title: Inhibition of Pin1 alleviates myocardial fibrosis and dysfunction in STZ-induced diabetic mice

Full Record
Other Related Research

Abstract

Therapeutic management of diabetic myocardial fibrosis remains an unsolved clinical problem. Pin1, a peptidyl–prolyl isomerase, impacts diverse cellular processes and plays a pivotal role in regulating cardiac pathophysiology. Here we investigate the potential mechanism of action of Pin1 and its role in diabetes-induced myocardial fibrosis and dysfunction in mice. Cardiac Pin1, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA) and extracellular matrix deposits (collagen I and III) are found to be increased in diabetic mice, which are effectively prevented by Pin1 inhibition by juglone. Pin1 inhibition alleviates cardiac fibrosis and dysfunction. In vitro, high glucose increases Pin1 expression with an accompanying increase in phospho-Akt (Ser 473), p-Smad2, p-Smad3, TGF-β1, and α-SMA in cardiac fibroblasts (CFs). These increases are effectively prevented by the inhibition of Pin1 by juglone. Furthermore, Pin1 inhibition inhibits HG-induced CF proliferation and migration. Our results indicate that Pin1 inhibition attenuates cardiac extracellular matrix deposition by regulating the phosphorylation of Akt, TGF-β1/Smads, MMP activities, and α-SMA expression in diabetic mice.

Authors:

Liu, Xue ^[1]; Liang, Ershun ^[1]; Song, Xiuhui ^[2]; Du, Zhanhui; Zhang, Yun ^[1]; Zhao, Yuxia ^[3]

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong 250012 (China)
The People's Hospital of JimoCity, Qingdao, Shandong 266200 (China)
Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012 (China)

Publication Date:: Fri Oct 07 00:00:00 EDT 2016

OSTI Identifier:: 22696632

Resource Type:: Journal Article

Journal Name:: Biochemical and Biophysical Research Communications

Additional Journal Information:: Journal Volume: 479; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; FIBROSIS; GROWTH FACTORS; INHIBITION; MATRICES; MICE; PLANT GROWTH

Citation Formats


                    Liu, Xue, Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, Liang, Ershun, Song, Xiuhui, Du, Zhanhui, Zhang, Yun, and Zhao, Yuxia. Inhibition of Pin1 alleviates myocardial fibrosis and dysfunction in STZ-induced diabetic mice.  United States: N. p., 2016. 
        Web.  doi:10.1016/J.BBRC.2016.09.050.

Copy to clipboard


                    Liu, Xue, Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, Liang, Ershun, Song, Xiuhui, Du, Zhanhui, Zhang, Yun, & Zhao, Yuxia. Inhibition of Pin1 alleviates myocardial fibrosis and dysfunction in STZ-induced diabetic mice.  United States.  https://doi.org/10.1016/J.BBRC.2016.09.050

Copy to clipboard


                    Liu, Xue, Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, Liang, Ershun, Song, Xiuhui, Du, Zhanhui, Zhang, Yun, and Zhao, Yuxia. 2016.  
        "Inhibition of Pin1 alleviates myocardial fibrosis and dysfunction in STZ-induced diabetic mice".  United States.  https://doi.org/10.1016/J.BBRC.2016.09.050.

Copy to clipboard


                    
@article{osti_22696632,

  title        = {Inhibition of Pin1 alleviates myocardial fibrosis and dysfunction in STZ-induced diabetic mice},

  author       = {Liu, Xue and Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012 and Liang, Ershun and Song, Xiuhui and Du, Zhanhui and Zhang, Yun and Zhao, Yuxia},

  abstractNote = {Therapeutic management of diabetic myocardial fibrosis remains an unsolved clinical problem. Pin1, a peptidyl–prolyl isomerase, impacts diverse cellular processes and plays a pivotal role in regulating cardiac pathophysiology. Here we investigate the potential mechanism of action of Pin1 and its role in diabetes-induced myocardial fibrosis and dysfunction in mice. Cardiac Pin1, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA) and extracellular matrix deposits (collagen I and III) are found to be increased in diabetic mice, which are effectively prevented by Pin1 inhibition by juglone. Pin1 inhibition alleviates cardiac fibrosis and dysfunction. In vitro, high glucose increases Pin1 expression with an accompanying increase in phospho-Akt (Ser 473), p-Smad2, p-Smad3, TGF-β1, and α-SMA in cardiac fibroblasts (CFs). These increases are effectively prevented by the inhibition of Pin1 by juglone. Furthermore, Pin1 inhibition inhibits HG-induced CF proliferation and migration. Our results indicate that Pin1 inhibition attenuates cardiac extracellular matrix deposition by regulating the phosphorylation of Akt, TGF-β1/Smads, MMP activities, and α-SMA expression in diabetic mice.},

  doi          = {10.1016/J.BBRC.2016.09.050},

  url          = {https://www.osti.gov/biblio/22696632},
  journal      = {Biochemical and Biophysical Research Communications},

  issn         = {0006-291X},

  number       = 1,

  volume       = 479,

  place        = {United States},

  year         = {Fri Oct 07 00:00:00 EDT 2016},

  month        = {Fri Oct 07 00:00:00 EDT 2016}

}

Copy to clipboard

Journal Article:

https://doi.org/10.1016/J.BBRC.2016.09.050

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

Similar records in OSTI.GOV collections:

Glaucocalyxin A attenuates angiotensin II-induced cardiac fibrosis in cardiac fibroblasts

Journal Article Su, Qianqian; Zhang, Yuan - Biochemical and Biophysical Research Communications

Highlights: • GLA inhibits Ang II-induced proliferation and migration of CFs. • GLA prevents the differentiation of CFs to myofibroblasts. • GLA inhibits the production of ECM and MMPs in Ang II-stimulated CFs. • GLA prevents TGF-β1/Smad3 pathway activation induced by Ang II in CFs. Glaucocalyxin A (GLA) is a natural ent-Kaurane diterpenoid that possesses cardioprotective effect. Recently, it has been reported that GLA inhibits liver and pulmonary fibrosis, whereas its role in cardiac fibrosis remains unknown. In the present study, we evaluated the effect of GLA on the pathogenesis of cardiac fibrosis in vitro. The results showed that GLAmore »« less
https://doi.org/10.1016/J.BBRC.2018.07.140
Obaculactone protects against bleomycin-induced pulmonary fibrosis in mice

Journal Article Wang, Xingqi; Ouyang, Zijun; You, Qian; ... - Toxicology and Applied Pharmacology

Idiopathic pulmonary fibrosis is a progressive, degenerative and almost irreversible disease. There is hardly an effective cure for lung damage due to pulmonary fibrosis. The purpose of this study was to evaluate the role of obaculactone in an already-assessed model of idiopathic pulmonary fibrosis induced by bleomycin administration. Mice were subjected to intratracheal instillation of bleomycin, and obaculactone was given orally after bleomycin instillation daily for 23 days. Treatment with obaculactone ameliorated body weight loss, lung histopathology abnormalities and pulmonary collagen deposition, with a decrease of the inflammatory cell number and the cytokine level in bronchoalveolar lavage fluid. Moreover, obaculactonemore »« less
https://doi.org/10.1016/J.TAAP.2016.05.005
TGF-β1-elevated TRPM7 channel regulates collagen expression in hepatic stellate cells via TGF-β1/Smad pathway

Journal Article Fang, Ling; Huang, Cheng; Meng, Xiaoming; ... - Toxicology and Applied Pharmacology

Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts plays a critical role in the development of liver fibrosis, since myofibroblasts are the key cells responsible for excessive deposition of ECM proteins. Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel with protein serine/threonine kinase activity, has been demonstrated to function in the proliferation of activated HSCs. Here, we investigated the functional role of TRPM7 in collagen deposition in activated HSC-T6 cells (a rat hepatic stellate cell line). TRPM7 mRNA and protein were measured by Real-time PCR and Western blot in TGF-β1-activated HSC-T6 cells in vitro. Results demonstrated that TRPM7more »« less
https://doi.org/10.1016/J.TAAP.2014.08.006
RIP2 deficiency attenuates cardiac hypertrophy, inflammation and fibrosis in pressure overload induced mice

Journal Article Zhao, Cui-Hua; Ma, Xiang; Guo, Hong-Yu; ... - Biochemical and Biophysical Research Communications

Although the pathological cardiac hypertrophy presents a leading cause of morbidity and mortality worldwide, our knowledge of the molecular mechanisms underlying the disease is still poor. Here, we reported that receptor-interacting serine/threonine-protein kinase 2 (RIP2), promoting pro-inflammatory gene expression, enhanced the pathological cardiac hypertrophy in animals. The effects of RIP2 on the cardiac hypertrophy triggered by pathological stimuli have not been fully investigated. In our study, mice were subjected to aortic banding (AB) surgery to explore the pathological, echocardiographic and molecular mechanisms. RIP2 expressed highly in cardiomyocytes after AB operation in wild type (WT) mice. RIP2-knockout (KO) attenuated cardiac hypertrophy,more »« less
https://doi.org/10.1016/J.BBRC.2017.07.035
Sphingomyelin phosphodiesterase 1 (SMPD1) mediates the attenuation of myocardial infarction-induced cardiac fibrosis by astaxanthin

Journal Article Shi, Yu; Lin, Peng; Wang, Xiaoning; ... - Biochemical and Biophysical Research Communications

Highlights: • Astaxanthin (ASX) attenuated cardiac fibrosis following myocardial infarction (MI). • MI-induced overaccumulation of myocardial ceramides was normalized by ASX. • Sphingomyelin phosphodiesterase 1 (SMPD1) mediates the anti-fibrotic effect of ASX. • SMPD1 knockout abrogated the cardioprotective functions of ASX. Uncontrolled cardiac fibrosis following myocardial infarction (MI) is a critical pathological change leading to heart failure. Current pharmacotherapies are limited by unsatisfactory efficacy and undesired systemic side effects. Astaxanthin (ASX) is a natural carotenoid with strong antioxidant and anti-inflammatory activities. The effects of ASX on MI-induced cardiac fibrosis and the underlying mechanisms remain largely unknown. In this study, aftermore »« less
https://doi.org/10.1016/J.BBRC.2018.06.054

Similar Records