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

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.

• Authors: Qing Mao, Cheng-Xi Lin, Xiu-Lin Liang, Jian-Shu Gao, Biao Xu
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 7 Issue 5 Pg. 1617-23 (May 2013) ISSN: 1791-3004 [Electronic] Greece
• PMID: 23450431 (Publication Type: Journal Article)

Chemical References

• Culture Media, Conditioned
• Cytokines
• Green Fluorescent Proteins
• Collagen
• integrin-linked kinase
• Protein Serine-Threonine Kinases

Topics

• Adenoviridae
• Animals
• Cell Proliferation (drug effects)
• Collagen (biosynthesis)
• Culture Media, Conditioned (pharmacology)
• Cytokines (genetics, metabolism)
• Electrocardiography
• Fibroblasts (drug effects, metabolism, pathology)
• Fibrosis
• Gene Expression Regulation (drug effects)
• Genetic Vectors
• Green Fluorescent Proteins (metabolism)
• Heart Function Tests
• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, drug effects, enzymology)
• Myocardial Infarction (enzymology, pathology)
• Myocardium (metabolism, pathology)
• Paracrine Communication (drug effects)
• Phenotype
• Protein Serine-Threonine Kinases (metabolism)
• Rats
• Rats, Sprague-Dawley
• Stroke Volume (drug effects)
• Transduction, Genetic
• Transfection