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MiR‐133a ameliorates cardiac stem cells survival and differentiation in Insulin2 mutant diabetic mice
Author(s) -
Chavali Vishalakshi,
Diaz Noel Leiberh,
Tyagi Suresh C,
Mishra Paras Kumar
Publication year - 2013
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.27.1_supplement.1151.2
Subject(s) - diabetic cardiomyopathy , stem cell , myocyte , medicine , cardiac fibrosis , cellular differentiation , biology , cardiomyopathy , fibrosis , heart failure , microbiology and biotechnology , genetics , gene
The Ins2 +/− (orthologous to human Insulin) mutation predisposes to diabetic complications and mitigates cardiac stem cell differentiation into cardiomyocytes that foster cardiomyopathy. MicroRNA (miR)‐133a, a muscle specific miRNA that regulates cardiac hypertrophy and fibrosis, is attenuated in diabetic hearts. However, the role of miR‐133a in cardiac stem cell survival and differentiation is unclear. We hypothesized that miR‐133a improves cardiac stem cell survival and differentiation and mitigates diabetic cardiomyopathy. To test the hypothesis, miR‐133a was overexpressed in WT (C57BL/6J) and diabetic Akita (Ins2+/‐) through lentivirus. The levels of miR‐133a, c‐kit and differentiation markers (Actn2, Oct4 and Tnnt2) were determined by individual miRNA assay, RT‐QPCR, Western blot and confocal microscopy in four groups: 1) WT, 2) Akita, 3) WT +miR‐133a, and 4) Akita + miR‐133a. The cardiac dysfunction was assessed by M‐Mode echocardiography. The results revealed that miR‐133a, c‐kit, Actn2, Oct4 and Tnnt2 were up regulated in Akita + miR‐133a as compared to Akita. The % FS is increased in Akita after miR‐133a treatment (Akita‐ 38.6±1.2; Akita +miR‐133a ‐ 50.8 ±5.1). These findings elicit a novel mechanism of miR‐133a mediated cardiac stem cell survival and differentiation and cardiac protection in diabetic mice.