Decrease IL33 expression in cardiac fibroblasts with high concentration of glucose leads to collagen IV production: role of PKCβ

Abstract

Diabetic cardiomyopathy (DiCM) is one of major complications of diabetes mellitus. Increase in collagen production by cardiac fibroblasts has been implicated in the development of the DiCM. In the present study, we assessed the role of PKCβ/IL‐33 pathway in the high glucose (HG)‐induced collagen production in cardiac fibroblasts.MethodsCultures cardiac fibroblasts were exposed to medium containing high concentration of glucose. The PKCβ phosphorylation status, IL33 and collagen production were assessed with Western or real‐time RT‐PCR.ResultsTreatment of the cardiac fibroblasts with HG led to a decrease in IL33 mRNA and protein expression which was associated with an increase in collagen IV production. Administration of IL‐33 prevented HG‐induced collagen IV production. Expose of cardiac fibroblasts to HG resulted in PKCβ;activation as indicated by increase in phosphorylation of PKCβ;Furthermore, inhibition of PKCβ;with an inhibitor prevented the increase in collagen IV production in HG‐treated cardiac fibroblasts.ConclusionOur results suggest that PKCβ/IL33 pathway plays an important role in regulation of HG‐induced collagen IV production in cardiac fibroblasts. (CIHR MOP‐81303)