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. 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

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Official URL: http://dx.doi.org/10.1038/srep33067

Abstract

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.

Item Type: Article
Uncontrolled Keywords: Angiotensin 1 receptor; HGF protein, human; Scatter factor; Smad7 protein; SMAD7 protein, human
Subjects: R Medicine > R Medicine (General)
T Technology > TA Engineering (General). Civil engineering (General)
Divisions: Faculty of Engineering
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 30 May 2018 05:27
Last Modified: 16 Dec 2019 03:36
URI: http://eprints.um.edu.my/id/eprint/18762

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