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

Peng Hu; Xiao Cen Zhang; Hai Bo Kong; Xun Xia; Bo Hu; Yuan Han Qin

doi:10.1038/labinvest.2014.149

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.

Authors

Peng Hu¹, Xiao Cen Zhang², Hai Bo Kong¹, Xun Xia¹, Bo Hu¹, Yuan Han Qin³

Affiliations

¹ Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
² 1] Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China [2] Department of Pediatrics, People's Hospital of Fuyang City, Fuyang, People's Republic of China.
³ Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.

PMID: 25437644
DOI: 10.1038/labinvest.2014.149

Abstract

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*

Substances

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