Neutral endopeptidase and natriuretic peptide receptors participate in the regulation of C-type natriuretic peptide expression in renal interstitial fibrosis

J Recept Signal Transduct Res. 2017 Feb;37(1):71-83. doi: 10.3109/10799893.2016.1155068. Epub 2016 Jun 8.

Abstract

The initiation and progression of renal interstitial fibrosis (RIF) is a complicated process in which many factors may play an activate role. Among these factors, C-type natriuretic peptide (CNP) is an endothelium-derived hormone and acts in a local, paracrine fashion to regulate vascular smooth muscle tone and proliferation. In this study, we established a rat model of unilateral ureteral obstruction (UUO). CNP expression tends to be higher immediately after ligation and declined at later time points, occurring predominantly in tubular epithelial cells. A high-level CNP may contribute to the elevated expression of natriuretic peptide receptor (NPR)-B in the early phase of UUO. However, the sustained expression of NPR-C and neutral endopeptidase (NEP) observed throughout the study period (that is up to 3 months) helps to, at least partly, explain the subsequent decline of CNP. Thus, NEP and NPRs participate in the regulation of CNP expression in RIF.

Keywords: C-type natriuretic peptide; natriuretic peptide receptor; neutral endopeptidase; renal interstitial fibrosis; unilateral ureteral obstruction.

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Fibrosis / genetics
  • Fibrosis / metabolism*
  • Fibrosis / pathology
  • Gene Expression Regulation, Developmental*
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Male
  • Natriuretic Peptide, C-Type / genetics
  • Natriuretic Peptide, C-Type / metabolism*
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Receptors, Atrial Natriuretic Factor / genetics
  • Receptors, Atrial Natriuretic Factor / metabolism*

Substances

  • Natriuretic Peptide, C-Type
  • Endopeptidases
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor B