Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-116946
Article
© Georg Thieme Verlag KG Stuttgart · New York

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

Ping Wang1, Meng Li2, Lei Dong3, Hui Chen5, Wei Su4, Yu-Peng Wang6
  • 1Cardiovascular Center, Affiliated Friendship Hospital, Capital Medical University, Beijing, 100050, P. R. China
  • 2Heart Department, Affiliated Daxing Hospital, Capital Medical University, Beijing, 100026, P. R. China
  • 3Heart Department, Civil Aviation General Hospital, Beijing 100123, P. R. China
  • 4Cardiovascular Department, Affiliated Liangxiang Hospital, Capital Medical University 102401, P. R. China
  • 5Cardiovascular Center, Affiliated Friendship Hospital, Capital Medical University Beijing, 100050, P. R. China
  • 6Healthcare Medical Center, Affiliated Friendship Hospital, Capital Medical University 100050, Beijing, P. R. China
Further Information

Publication History

Publication Date:
11 September 2017 (eFirst)

Abstract

Relaxin (Rlx) is known to antagonize diabetic cardiac fibrosis. However, its mechanism is poorly understood. Protein kinase Cδ (PKCδ) plays a crucial role in diabetic cardiomyopathy (DCM). This study explored the involvement of PKCδ 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 pre-treated for 1 week with human recombinant relaxin (rhRlx, 30 μg/kg.d), were assessed to detect cardiac fibrosis and PKCδ 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 PKCδ. The effects of rhRlx and PKCδ 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 cardiac fibroblasts and the expression of collagen I. The expression of PKCδ was regulated by Rlx in diabetic rats and cardiac fibroblasts under HG condition. The effects of Rlx upon the proliferation and differentiation of cardiac fibroblasts 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 PKCδ.