Exogenous C-type natriuretic peptide infusion ameliorates unilateral ureteral obstruction-induced tubulointerstitial fibrosis in rats

Lab Invest. 2015 Mar;95(3):263-72. doi: 10.1038/labinvest.2014.149. Epub 2014 Dec 1.


Although many experimental therapeutic roles for C-type natriuretic peptide (CNP) have been documented in the field of cardiovascular and pulmonary-vascular disease, the therapeutic uses of CNP to nephropathies are not as well documented. In this study, we established a rat model of unilateral ureteral obstruction (UUO) to observe the beneficial effects of CNP on tubulointerstitial fibrosis (TIF). In UUO rats, CNP administration induced a significant increase in plasma CNP levels, and caused a significant decrease in blood urea nitrogen and creatinine levels. In addition, CNP infusion also alleviated the pathological lesions and collagen IV accumulation in the obstructed kidneys through downregulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 expression. In conclusion, exogenous CNP infusion can ameliorate UUO-induced TIF in rats. However, the use of CNP as a therapeutic agent requires further evaluation before being considered for human TIF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism
  • Fibrosis
  • Gene Expression / drug effects
  • Infusions, Intravenous
  • Kidney Diseases / etiology
  • Kidney Diseases / prevention & control*
  • Kidney Tubules / drug effects*
  • Kidney Tubules / pathology
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Natriuretic Peptide, C-Type / administration & dosage*
  • Natriuretic Peptide, C-Type / blood
  • Natriuretic Peptide, C-Type / genetics
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Ureteral Obstruction / complications*


  • Collagen Type IV
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Natriuretic Peptide, C-Type
  • Matrix Metalloproteinase 9