Ablation of mmp9 induces survival and differentiation of cardiac stem cells into cardiomyocytes in the heart of diabetics: A role of extracellular matrix

Paras Kumar Mishra, Vishalakshi Chavali, Naira Metreveli, Suresh C. Tyagi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The contribution of extracellular matrix (ECM) to stem cell survival and differentiation is unequivocal, and matrix metalloproteinase-9 (MMP9) induces ECM turn over; however, the role of MMP9 in the survival and differentiation of cardiac stem cells is unclear. We hypothesize that ablation of MMP9 enhances the survival and differentiation of cardiac stem cells into cardiomyocytes in diabetics. To test our hypothesis, Ins2 +/- Akita, C57 BL/6J, and double knock out (DKO: Ins2 +/-/MMP9 -/-) mice were used. We created the DKO mice by deleting the MMP9 gene from Ins2 +/-. The above 3 groups of mice were genotyped. The activity and expression of MMP9 in the 3 groups were determined by in-gel gelatin zymography, Western blotting, and confocal microscopy. To determine the role of MMP9 in ECM stiffness (fibrosis), we measured collagen deposition in the histological sections of hearts using Masson's trichrome staining. The role of MMP9 in cardiac stem cell survival and differentiation was determined by co-immunoprecipitation (co-IP) of MMP9 with c-kit (a marker of stem cells) and measuring the level of troponin I (a marker of cardiomyocytes) by confocal microscopy in the 3 groups. Our results revealed that ablation of MMP9 (i) reduces the stiffness of ECM by decreasing collagen accumulation (fibrosis), and (ii) enhances the survival (elevated c-kit level) and differentiation of cardiac stem cells into cardiomyocytes (increased troponin I) in diabetes. We conclude that inhibition of MMP9 ameliorates stem cell survival and their differentiation into cardiomyocytes in diabetes.

Original languageEnglish (US)
Pages (from-to)353-360
Number of pages8
JournalCanadian journal of physiology and pharmacology
Volume90
Issue number3
DOIs
StatePublished - Mar 1 2012

Fingerprint

Matrix Metalloproteinase 9
Cardiac Myocytes
Extracellular Matrix
Stem Cells
Cell Survival
Troponin I
Confocal Microscopy
Cell Differentiation
Fibrosis
Collagen
Gelatin
Immunoprecipitation
Western Blotting
Gels
Staining and Labeling

Keywords

  • Akita
  • C-kit
  • Diabetes
  • Differentiation
  • Fibrosis
  • Heart
  • Mmp9
  • Troponin i

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

Ablation of mmp9 induces survival and differentiation of cardiac stem cells into cardiomyocytes in the heart of diabetics : A role of extracellular matrix. / Mishra, Paras Kumar; Chavali, Vishalakshi; Metreveli, Naira; Tyagi, Suresh C.

In: Canadian journal of physiology and pharmacology, Vol. 90, No. 3, 01.03.2012, p. 353-360.

Research output: Contribution to journalArticle

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