Regulative Effects Of C-type Natriuretic Peptide On Tubulointerstitial Fibrosis Via Matrix Metalloproteinases/Tissue Inhibitors Of Metalloproteinases Signaling

Background and objectiveThe study presented herein was designed as a first demonstration of the regulativeeffects of C-type natriuretic peptide (CNP) on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) expression in unilateral ureteralobstruction (UUO) rats.MethodsThe continuous changes of CNP, MMP-2, MMP-9, TIMP-1, TIMP-2and type IVcollagen (Col-IV) expression were determined in the obstructed rat kidneys at3days,1,2, and3months post-UUO respectively.ResultsAccording to the real-time PCR analysis, CNP, MMP-2and MMP-9mRNAexpression in the obstructed kidneys were significantly higher compared to every timecorresponding sham-operated rats (SOR), and progressively decreased over time. Incontrast, in the obstructed kidneys collected2and3months post-UUO, the higherTIMP-1and TIMP-2mRNA expression were observed in comparison to thecorresponding SOR group. The above trends of CNP, MMP-2, MMP-9, TIMP-1, andTIMP-2transcripts were confirmed by their protein expression based onimmunohistochemistry and western blot, and finally contributed to the progressiveelevated Col-IV expression in the obstructed kidneys throughout the entire studyperiod. ConclusionsProgressive decrease of CNP expression may be a major contribution toMMPs/TIMPs dysmetabolism and extracellular matrix remodeling.