Overexpressed C-type natriuretic peptide serves as an early compensatory response to counteract extracellular matrix remodeling in unilateral ureteral obstruction rats

Mol Biol Rep. 2013 Feb;40(2):1429-41. doi: 10.1007/s11033-012-2186-7. Epub 2012 Oct 17.


Although the mechanism underlying C-type natriuretic peptide (CNP) beneficial effects is not entirely understood, modulating the expression of matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) may play an important role. The study presented herein was designed as a first demonstration of the regulative effects of CNP on MMPs/TIMPs expression in unilateral ureteral obstruction (UUO) rats. The continuous changes of CNP, MMP-2, MMP-9, TIMP-1, TIMP-2 and type IV collagen (Col-IV) expression were determined in the obstructed rat kidneys at 3 days, 1, 2, and 3 months post-UUO respectively. According to the real-time PCR analysis, CNP, MMP-2 and MMP-9 mRNA expression in the obstructed kidneys were significantly higher compared to every time corresponding SOR, and progressively decreased over time. In contrast, in the obstructed kidneys collected 2 and 3 months post-UUO, the higher TIMP-1 and TIMP-2 mRNA expression were observed in comparison to the corresponding SOR group. The above trends of CNP, MMP-2, MMP-9, TIMP-1, and TIMP-2 transcripts were confirmed by their protein expression based on immunohistochemistry and western blot, and finally contributed to the progressive elevated Col-IV expression in the obstructed kidneys throughout the entire study period. Overexpressed CNP may be an early compensatory response to counteract extracellular matrix remodeling in UUO rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism
  • Epithelial-Mesenchymal Transition
  • Extracellular Matrix / metabolism*
  • Fibrosis
  • Gene Expression
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Natriuretic Peptide, C-Type / genetics*
  • Natriuretic Peptide, C-Type / metabolism
  • Organ Size
  • Rats
  • Rats, Wistar
  • 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 / metabolism*
  • Ureteral Obstruction / pathology


  • Collagen Type IV
  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Natriuretic Peptide, C-Type
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat