Relaxin Inhibits Cardiac Fibrosis in Diabetic Rats: Roles of Protein Kinase Cδ

Relaxin (Rlx) is known to antagonize diabetic cardiac fibrosis. However, its mechanism is poorly understood. Protein kinase C delta (PKC delta) plays a crucial role in diabetic cardiomyopathy (DCM). This study explored the involvement of PKC delta in Rlx's capacity of suppressing cardiac fibrosis in a rat model of type 2 diabetes mellitus (DM). Type 2 DM of 8-week-old male Sprague-Dawley (SD) rats was induced by a high-fat diet and the injection of streptozocin (STZ, 40 mg/kg). Fourteen-week-old rats with DM and rats in control group which were pretreated for 1 week with human recombinant relaxin (rhRlx, 30 mu g/kg.d), were assessed to detect cardiacfibrosis and PKC delta expression with Western blot. Cardiac fibroblasts of neonatal rats were treated for 72 h with rhRlx (100 ng/ml) under high glucose (HG). Western blot was utilized for detecting the membranous and cytoplasmic protein expressions of PKC delta. The effects of rhRlx and PKC delta inhibitor (rottlerin) were assessed either alone or in combination on the HG-induced proliferation and differentiation of cardiac fibroblasts and the release of collagen I. Rlx treatment inhibited the differentiation of cardiacfibroblasts and the expression of collagen I. The expression of PKC delta was regulated by Rlx in diabetic rats and cardiac fibroblasts under HG condition. The effects of Rlx upon the proliferation and differentiation of cardiacfibroblasts and the excretion of collagen I under HG were blunted by rottlerin. Rlx suppressed cardiac fibrosis in type 2 diabetic rats. This beneficial effect was associated with its ability of modulating the expression of PKC delta.