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, DOI https://doi.org/10.1038/srep33067.
Full text not available from this repository.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 |
|---|---|
| Funders: | National Natural Science Foundation of China [11602191, 11372243, 11532009, 11522219], International Science and Technology Cooperation Program of China [2013DFG02930], Key Program for International S and T Cooperation Projects of Shaanxi [2013KW33-01], China Postdoctoral Science Foundation (2013M540742), Research Fund for the Doctoral Program of Higher Education of China (20130201120071) the Young Talent Fund of University Association for Science and Technology in Shaanxi, China (20150101), University of Malaya from the Ministry of Education Malaysia: High Impact Research Grant [UM.C/HIR/MOHE/ENG/44] and the UMRG Grant [RP040A-15HTM] |
| 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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