Staff View: Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7

Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7

Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis therapy, due to their potential ability of inhibiting cardiac myofibroblast differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved in their effects remains elusive. To explore this, it is necessary...

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Main Authors:	Yong, K.W., Li, Y., Liu, F., Gao, B., Lu, T.J., Wan Abas, Wan Abu Bakar, Wan Kamarul Zaman, Wan Safwani, Pingguan-Murphy, Belinda, Ma, Y., Xu, F., Huang, G.
Format:	Article
Published:	Nature Publishing Group 2016
Subjects:	R Medicine (General) TA Engineering (General). Civil engineering (General)
Online Access:	http://eprints.um.edu.my/18762/ http://dx.doi.org/10.1038/srep33067
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spelling	my.um.eprints.187622019-12-16T03:36:01Z http://eprints.um.edu.my/18762/ Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7 Yong, K.W. Li, Y. Liu, F. Gao, B. Lu, T.J. Wan Abas, Wan Abu Bakar Wan Kamarul Zaman, Wan Safwani Pingguan-Murphy, Belinda Ma, Y. Xu, F. Huang, G. R Medicine (General) TA Engineering (General). Civil engineering (General) Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis therapy, due to their potential ability of inhibiting cardiac myofibroblast differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved in their effects remains elusive. To explore this, it is necessary to develop an in vitro cardiac fibrosis model that incorporates pore size and native tissue-mimicking matrix stiffness, which may regulate cardiac myofibroblast differentiation. In the present study, collagen coated polyacrylamide hydrogel substrates were fabricated, in which the pore size was adjusted without altering the matrix stiffness. Stiffness is shown to regulate cardiac myofibroblast differentiation independently of pore size. Substrate at a stiffness of 30 kPa, which mimics the stiffness of native fibrotic cardiac tissue, was found to induce cardiac myofibroblast differentiation to create in vitro cardiac fibrosis model. Conditioned medium of hMSCs was applied to the model to determine its role and inhibitory mechanism on cardiac myofibroblast differentiation. It was found that hMSCs secrete hepatocyte growth factor (HGF) to inhibit cardiac myofibroblast differentiation via downregulation of angiotensin II type 1 receptor (AT1R) and upregulation of Smad7. These findings would aid in establishment of the therapeutic use of hMSCs in cardiac fibrosis therapy in future. Nature Publishing Group 2016 Article PeerReviewed Yong, K.W. and Li, Y. and Liu, F. and Gao, B. and Lu, T.J. and Wan Abas, Wan Abu Bakar and Wan Kamarul Zaman, Wan Safwani and Pingguan-Murphy, Belinda and Ma, Y. and Xu, F. and Huang, G. (2016) Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7. Scientific Reports, 6 (1). p. 33067. ISSN 2045-2322 http://dx.doi.org/10.1038/srep33067 doi:10.1038/srep33067
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine (General) TA Engineering (General). Civil engineering (General)
spellingShingle	R Medicine (General) TA Engineering (General). Civil engineering (General) Yong, K.W. Li, Y. Liu, F. Gao, B. Lu, T.J. Wan Abas, Wan Abu Bakar Wan Kamarul Zaman, Wan Safwani Pingguan-Murphy, Belinda Ma, Y. Xu, F. Huang, G. Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7
description	Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis therapy, due to their potential ability of inhibiting cardiac myofibroblast differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved in their effects remains elusive. To explore this, it is necessary to develop an in vitro cardiac fibrosis model that incorporates pore size and native tissue-mimicking matrix stiffness, which may regulate cardiac myofibroblast differentiation. In the present study, collagen coated polyacrylamide hydrogel substrates were fabricated, in which the pore size was adjusted without altering the matrix stiffness. Stiffness is shown to regulate cardiac myofibroblast differentiation independently of pore size. Substrate at a stiffness of 30 kPa, which mimics the stiffness of native fibrotic cardiac tissue, was found to induce cardiac myofibroblast differentiation to create in vitro cardiac fibrosis model. Conditioned medium of hMSCs was applied to the model to determine its role and inhibitory mechanism on cardiac myofibroblast differentiation. It was found that hMSCs secrete hepatocyte growth factor (HGF) to inhibit cardiac myofibroblast differentiation via downregulation of angiotensin II type 1 receptor (AT1R) and upregulation of Smad7. These findings would aid in establishment of the therapeutic use of hMSCs in cardiac fibrosis therapy in future.
format	Article
author	Yong, K.W. Li, Y. Liu, F. Gao, B. Lu, T.J. Wan Abas, Wan Abu Bakar Wan Kamarul Zaman, Wan Safwani Pingguan-Murphy, Belinda Ma, Y. Xu, F. Huang, G.
author_facet	Yong, K.W. Li, Y. Liu, F. Gao, B. Lu, T.J. Wan Abas, Wan Abu Bakar Wan Kamarul Zaman, Wan Safwani Pingguan-Murphy, Belinda Ma, Y. Xu, F. Huang, G.
author_sort	Yong, K.W.
title	Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7
title_short	Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7
title_full	Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7
title_fullStr	Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7
title_full_unstemmed	Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7
title_sort	paracrine effects of adipose-derived stem cells on matrix stiffness-induced cardiac myofibroblast differentiation via angiotensin ii type 1 receptor and smad7
publisher	Nature Publishing Group
publishDate	2016
url	http://eprints.um.edu.my/18762/ http://dx.doi.org/10.1038/srep33067
_version_	1654960684058804224
score	13.211869

Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7

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