PAI-1,TIMP-1 gene expression in renal tubulointerstitial fibrosis of ureteral obstruction and the interfering effects of HGF treatment
- VernacularTitle:PAI-1和TIMP-1基因在肾小管间质纤维化中的表达及HGF的干预作用
- Author:
Yunjian HUANG
;
Yuanning ZHANG
;
Yiqin WANG
;
Jinghong ZHAO
;
Tangjun YANG
;
Wenqi CAI
- Publication Type:Journal Article
- Keywords:
Plasminogen activator inhibitor 1;
Tissue-inhibitor of metalloproteinase-1;
Transforming growth factor beta;
Hepatocyte growth factor;
Kidney tubules;
Fibrosis
- From:
Chinese Journal of Pathophysiology
1999;0(09):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM: The aim of this study was to determine the relationship between PAI-1,TIMP-1 gene expression and renal tubulointerstitial fibrosis(TIF) of ureteral obstruction ,and the interfering effects of hepatocyte growth factor (HGF) treatment. METHODS: Sixty rats were divided into normal control, sham operation,unilateral ureteral obstruction(UUO),and rhHGF treated groups (received 0 5 mg?kg -1 ?d -1 HGF for twenty-one days), and were sacrificed at postoperative day 3, 7, 14, 21. The levels of PAI-1, TIMP-1 mRNA were measured by RT-PCR. MMP2 and MMP9 activities were detected by substrate zymography, and renal fibrosis was assessed by measuring tissue hydroxyproline. RESULTS: Compared to controls, expression levels of PAI-1,TIMP-1 mRNA were significantly increased in UUO rats, and this was accompanied by decreased activities of MMP2 and MMP9 and increase in tissue hydroxyproline content. HGF treatment significantly decreased expressions of PAI-1, TIMP-1 mRNA, increased MMP2 and MMP9 activities,and decreased tissue hydroxyproline content in the obstructive kidney. CONCLUSIONS: These results indicate that the increases in PAI-1, TIMP-1 mRNA expression may be the major cause of sustained decreased matrix degradation during the development of tubulointerstitial fibrosis after unilateral ureteral obstruction. rhHGF efficiently ameliorates renal tubulointerstitial injury by the reduction of PAI-1,TIMP-1 mRNA expression, and increasing MMP2, MMP9 activities. [
