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Title: Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality

Abstract

Highlights: {yields} Deletion of Dicer in vascular smooth muscle cells(VSMCs) leads to embryonic mortality. {yields} Loss of Dicer in VSMCs leads to developmental delay. {yields} Loss of Dicer in VSMCs leads to hemorrhage in various organs including brain, skin and liver. {yields} Loss of Dicer in VSMCs leads to vascular wall remodeling. {yields} Loss of Dicer in VSMCs dysregulates the expression of miRNA and VSMC marker genes. -- Abstract: Dicer is a RNAase III enzyme that cleaves double stranded RNA and generates small interfering RNA (siRNA) and microRNA (miRNA). The goal of this study is to examine the role of Dicer and miRNAs in vascular smooth muscle cells (VSMCs). We deleted Dicer in VSMCs of mice, which caused a developmental delay that manifested as early as embryonic day E12.5, leading to embryonic death between E14.5 and E15.5 due to extensive hemorrhage in the liver, brain, and skin. Dicer KO embryos showed dilated blood vessels and a disarray of vascular architecture between E14.5 and E15.5. VSMC proliferation was significantly inhibited in Dicer KOs. The expression of VSMC marker genes were significantly downregulated in Dicer cKO embryos. The vascular structure of the yolk sac and embryo in Dicer KOs was lost tomore » an extent that no blood vessels could be identified after E15.5. Expression of most miRNAs examined was compromised in VSMCs of Dicer KO. Our results indicate that Dicer is required for vascular development and regulates vascular remodeling by modulating VSMC proliferation and differentiation.« less

Authors:
 [1];  [2];  [1];  [1]
  1. Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States)
  2. Department of Pathology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States)
Publication Date:
OSTI Identifier:
22204911
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 408; Journal Issue: 3; Other Information: Copyright (c) 2011 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; BLOOD VESSELS; BRAIN; EMBRYOS; ENZYMES; GENES; HEMORRHAGE; LIVER; MICE; MORTALITY; MUSCLES; RNA; SKIN

Citation Formats

Pan, Yaoqian, Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, Balazs, Louisa, Tigyi, Gabor, Yue, Junming, and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163. Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.02.119.
Pan, Yaoqian, Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, Balazs, Louisa, Tigyi, Gabor, Yue, Junming, & Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163. Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality. United States. https://doi.org/10.1016/J.BBRC.2011.02.119
Pan, Yaoqian, Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, Balazs, Louisa, Tigyi, Gabor, Yue, Junming, and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163. 2011. "Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality". United States. https://doi.org/10.1016/J.BBRC.2011.02.119.
@article{osti_22204911,
title = {Conditional deletion of Dicer in vascular smooth muscle cells leads to the developmental delay and embryonic mortality},
author = {Pan, Yaoqian and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163 and Balazs, Louisa and Tigyi, Gabor and Yue, Junming and Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163},
abstractNote = {Highlights: {yields} Deletion of Dicer in vascular smooth muscle cells(VSMCs) leads to embryonic mortality. {yields} Loss of Dicer in VSMCs leads to developmental delay. {yields} Loss of Dicer in VSMCs leads to hemorrhage in various organs including brain, skin and liver. {yields} Loss of Dicer in VSMCs leads to vascular wall remodeling. {yields} Loss of Dicer in VSMCs dysregulates the expression of miRNA and VSMC marker genes. -- Abstract: Dicer is a RNAase III enzyme that cleaves double stranded RNA and generates small interfering RNA (siRNA) and microRNA (miRNA). The goal of this study is to examine the role of Dicer and miRNAs in vascular smooth muscle cells (VSMCs). We deleted Dicer in VSMCs of mice, which caused a developmental delay that manifested as early as embryonic day E12.5, leading to embryonic death between E14.5 and E15.5 due to extensive hemorrhage in the liver, brain, and skin. Dicer KO embryos showed dilated blood vessels and a disarray of vascular architecture between E14.5 and E15.5. VSMC proliferation was significantly inhibited in Dicer KOs. The expression of VSMC marker genes were significantly downregulated in Dicer cKO embryos. The vascular structure of the yolk sac and embryo in Dicer KOs was lost to an extent that no blood vessels could be identified after E15.5. Expression of most miRNAs examined was compromised in VSMCs of Dicer KO. Our results indicate that Dicer is required for vascular development and regulates vascular remodeling by modulating VSMC proliferation and differentiation.},
doi = {10.1016/J.BBRC.2011.02.119},
url = {https://www.osti.gov/biblio/22204911}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 408,
place = {United States},
year = {Fri May 13 00:00:00 EDT 2011},
month = {Fri May 13 00:00:00 EDT 2011}
}