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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Nature Publishing Group
2016
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| 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. |
| collection | UM |
| 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. |
| first_indexed | 2024-03-06T05:46:16Z |
| format | Article |
| id | um.eprints-18762 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T05:46:16Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | 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, DOI https://doi.org/10.1038/srep33067 <https://doi.org/10.1038/srep33067>. http://dx.doi.org/10.1038/srep33067 doi:10.1038/srep33067 |
| 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 |
| title | 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_short | 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 |
| topic | R Medicine (General) TA Engineering (General). Civil engineering (General) |
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