title: 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: Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, PR China.
authors: Qing
authors: Q
authors: Mao
authors: Cheng-Xi
authors: CX
authors: Lin
authors: Xiu-Lin
authors: XL
authors: Liang
authors: Jian-Shu
authors: JS
authors: Gao
authors: Biao
authors: B
authors: Xu
mesh_terms: D000256:Adenoviridae; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004562:Electrocardiography; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006334:Heart Function Tests; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019899:Paracrine Communication / Q000187:drug effects; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects; D014161:Transduction, Genetic; D014162:Transfection; D000099200:Scaffold Protein ILK
chemical_list: D003094:Collagen; D017077:Culture Media, Conditioned; D016207:Cytokines; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK