Mesenchymal stem cells overexpressing integrin-linked kinase attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions

Mao,Qing; Lin,Cheng-Xi; Liang,Xiu-Lin; Gao,Jian-Shu; Xu,Biao

doi:10.3892/mmr.2013.1348

Mesenchymal stem cells overexpressing integrin-linked kinase attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions

Authors:
- Qing Mao
- Cheng-Xi Lin
- Xiu-Lin Liang
- Jian-Shu Gao
- Biao Xu
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Affiliations: Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, P.R. China, Department of Gerontology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Suzhou University, Changzhou 213000, P.R. China
Published online on: February 28, 2013 https://doi.org/10.3892/mmr.2013.1348
Pages: 1617-1623

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Abstract

Mesenchymal stem cells (MSCs) transfected by integrin-linked kinase (ILK) transplantation may improve the function and compliance of the post-infarct cardiac ventricle. We investigated the effect of ILK-modified MSC contiditioned medium (ILK-MSC-CM) on the proliferation of cardiac fibroblasts (CFBs) and collagen synthesis in vitro and in vivo. Myocardial infarction (MI)-induced animals received mesenchymal stem cell conditioned medium (MSC-CM), ILK-MSC-CM, or complete medium alone, subepicardially. A group of animals with MI and no other former intervention served as controls. ILK-MSC-CM inhibited CFB proliferation, reduced the gene expression of type I (Col1a1) and type III collagen (Col3a1), tissue inhibitors of metalloproteinase‑1 (TIMP-1) and ‑2 (TIMP-2), α smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF). It also increased the gene expression of matrix metalloproteinase‑2 (MMP‑2) and -9 (MMP‑9), as measured by qRT-PCR. Four weeks after the left anterior descending (LAD) coronary artery ligation, echocardiographic analysis demonstrated preserved cardiac geometry and contractility in the ILK-MSC-CM treated animals. Decreased infarct size and reduced fibrosis were observed in the ILK-MSC-CM group. Overexpression of ILK regulates paracrine actions of MSCs, and ILK-MSC-CM attenuates CFB proliferation and collagen synthesis through paracrine actions in vitro and in vivo.

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