Lipocalin-2 mediated myocardial extracellular matrix remodeling is correlated with Akt/P38 activity in hearts

Abstract

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.