Overexpressed C-type natriuretic peptide serves as an early compensatory response to counteract extracellular matrix remodeling in unilateral ureteral obstruction rats.
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.
Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, No. 218 Ji-Xi Road, Hefei, 230022, People's Republic of China. hupeng28@sohu.com
Peng
P
Hu
Jing
J
Wang
Xue Qi
XQ
Zhao
Bo
B
Hu
Ling
L
Lu
Yuan Han
YH
Qin
D000818:Animals; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism*; D005355:Fibrosis; D015870:Gene Expression; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology
D024141:Collagen Type IV; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020098:Natriuretic Peptide, C-Type; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat