Relaxin Ameliorates Renal Fibrosis and Expression of Endothelial Cell Transition Markers in Rats of Isoproterenol-Induced Heart Failure

Biol Pharm Bull. 2017;40(7):960-966. doi: 10.1248/bpb.b16-00882.

Abstract

There may be cardio-renal interactions in rats of isoproterenol-induced heart failure, which may be associated with renal fibrosis and endothelial-to-mesenchymal transition (EndMT). Since its discovery, relaxin (RLX) which was regarded as a reproductive hormone for a long time, is recently considered an effective antifibrotic hormone in cardiac and renal fibrosis. We studied whether RLX diminished renal fibrosis in rats of isoproterenol (Iso)-induced heart failure and investigated the mechanism. Fifty male Sprague-Dawley rats were separated into five groups for treatment: control; Iso subcutaneously injection to induce heart failure, which led to renal fibrosis; RLX subcutaneously injection at low, medium and high dose (0.2, 2, 20 µg·kg-1·d-1 for 21 d). Indices of cardiac function and organ fibrosis were examined. Expression and changes in levels of collagen, cluster of differentiation 31 (CD31), α-smooth muscle actin (SMA), and transforming growth factor β (TGF-β) were measured in renal tissues. In rats with heart failure induced by Iso, treatment with RLX significantly ameliorated cardiac function and inhibited cardiac and renal fibrosis. RLX decreased renal collagen types I and III deposition, increased CD31 expression, and decreased the expression of α-SMA and TGF-β, thereby possibly indicating inhibited renal EndMT in kidneys. Iso-induced heart and renal fibrosis was inhibited even greater with high-dose RLX, so the antifibrotic effect of RLX may be dose-related. In conclusion, RLX may ameliorate renal fibrosis in rats of Iso-induced heart failure, and it is infered that prevention of the EndMT may be one of the possible potential signaling pathways.

Keywords: endothelial–mesenchymal transition; heart failure; relaxin; renal fibrosis.

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Blotting, Western
  • Collagen / metabolism
  • Dose-Response Relationship, Drug
  • Endothelial Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Fibrosis
  • Heart Failure / chemically induced*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Heart Function Tests
  • Isoproterenol / toxicity*
  • Kidney Diseases / prevention & control*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Relaxin / metabolism*

Substances

  • Biomarkers
  • Relaxin
  • Collagen
  • Isoproterenol