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Lipocalin‐2 mediated myocardial extracellular matrix remodeling is correlated with Akt/P38 activity in hearts
Author(s) -
Yang Bo,
Vanhoutte Paul M,
Wang Yu
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.1114.4
Subject(s) - lipocalin , extracellular matrix , protein kinase b , extracellular , matrix metalloproteinase , microbiology and biotechnology , chemistry , intracellular , medicine , endocrinology , phosphorylation , biology , biochemistry
Lipocalin‐2, a 25‐kDa glycoprotein secreted by adipocytes, belongs to the diversified lipocalin family. Although its physiological functions remain elusive, the expression of this protein is up‐regulated or rapidly induced under various pathological conditions. The impact of lipocalin‐2 on extracellular matrix (ECM) remodeling was determined in cardiac cells of wild type rats. Incubation of primary cultured fibroblasts with recombinant lipocalin‐2 promoted both intracellular collagen expression and extracellular collagen secretion. Up‐regulation of collagen production was also shown in infarcted cardiac tissues after permanent coronary artery ligation in wild type mice, which was positively correlated with enhanced levels of lipocalin‐2 in serum or the infracted heart tissues. The phosphorylation levels of Akt and/or P‐38 were significantly decreased by lipocalin‐2 treatment in primary cultured cardiomyocytes, fibroblasts or infarcted heart tissues. Gelatin zymography analysis of matrix metalloproteinase‐2 (MMP‐2) activity in conditioned medium collected from fibroblasts demonstrated that lipocalin‐2 treatment significantly induced MMP‐2 activity. These results demonstrate that lipocalin‐2 plays a role in mediating myocardial ECM remodeling and that the Akt/P‐38 pathways mediate these effects of the adipokine.