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GATA‐4 Gene Transfer Increases Mesenchymal Stem Cell Mediated Myocardial Salvage through miRNA Regulation and Bioactive Molecules Migration between Cells
Author(s) -
Xu Meifeng,
Yu Bin,
Pasha Zeeshan,
Wang Yigang
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.856.5
Subject(s) - mesenchymal stem cell , microrna , stem cell , angiogenesis , microbiology and biotechnology , cardiac function curve , arteriogenesis , cancer research , chemistry , biology , medicine , gene , heart failure , biochemistry
We hypothesized that GATA‐4 enhanced mesenchymal stem cell (MSC) mediated ischemic heart repair via regulating miRNA (miR). Methods and Results GATA‐4 was transduced into MSC (MSC GATA‐4 ) using the murine stem cell virus retroviral expression system. Overexpression of GATA‐4 downregulated miR‐15 family (miR‐15b, miR‐16, and miR‐195) and upregulating miR‐221/222 in MSC assayed using miR microarray and quantitative RT‐PCR. GATA‐4 significantly increased MSC survival evaluated by counting Annexin‐V + cell and by MTT intake. MSC GATA‐4 markedly protected myocytes (CM) against ischemic injury examined through measurements of LDH release, MTT intake, and Annexin‐V staining. Fluorescence in situ hybridization and immunostaining results showed that miR‐221 as well as Bcl‐w and VEGF, two proteins of target genes of miR‐15 family, were transferred from MSC to CM. Gap junctions were observed between CM and MSC in a co‐culture system. The rats transplanted MSC GATA‐4 following left anterior descending coronary artery ligation showed a significantly improved cardiac function by echocardiography. Furthermore, histological studies revealed reduced infarction size and increased angiogenesis. Conclusions Overexpression of GATA‐4 regulates miR expression in MSC, which plays an important role in MSC GATA‐4 mediated salutary effects on improving cardiac function and cardioprotection.