Hen Xue1, Liang Chen, Jun-ming Fan, Zi Li. 1. Department of Nephrology, West China Hosipital, Shichuan University, Chengdu 610041, China.
Abstract
OBJECTIVE: To investigate the dynamic changes of MMP-9 and TIMP-1 expressions in rat unilateral ureteral obstruction (UUO) model, and to explore the role of MMP-9 and TIMP-1 in tubular epithelialmyofibroblast transdifferentiation. METHODS: Sixty-four male rats were randomly allocated to sham UUO group and UUO group. Rats were sacrificed respectively at 3, 7, 14 and 21 days after UUO or sham-surgery. The expression levels of MMP-9, TIMP-1, alpha-smooth muscle actin (alpha-SMA) and fibronectin (FN) were examined by immunohistochemistry staining at each time point. RESULTS: In UUO rats, the disruption of renal tubular basement membrane (TBM) in PAS staining was found at day 3 after operation. At postoperative day 14 and 21, the TBM was observed to be thickened and wrinkled with partial and extensive disruption. On day 3 after UUO, the expressions of alpha-SMA and FN in tubulointerstitium were obviously increased. On day 7, some tubular epithelial cells also expressed alpha-SMA. In UUO rats, the strong positive expression of MMP-9 in renal tubulointerstitium was found at day 3 after operation and the expression peaked in tubulointerstitium at day 7, then decreased gradually. (4) In UUO rats, TIMP-1 expression in renal tubulointerstitium was increased progressively starting from day 3 to day 21. (5) The expression of MMP-9 in renal tubulointerstitium was significantly associated with the positive area of alpha-SMA and the disruption of TBM. CONCLUSION: The expression levels of MMP-9 and TIMP-1 relate closely to the disruption of TBM. TBM structural and functional integrity depends on many intricate interactions between MMP-9 and TIMP-1, which may play an important role in tubular epithelialmyofibroblast transdifferentiation.
OBJECTIVE: To investigate the dynamic changes of MMP-9 and TIMP-1 expressions in ratunilateral ureteral obstruction (UUO) model, and to explore the role of MMP-9 and TIMP-1 in tubular epithelialmyofibroblast transdifferentiation. METHODS: Sixty-four male rats were randomly allocated to sham UUO group and UUO group. Rats were sacrificed respectively at 3, 7, 14 and 21 days after UUO or sham-surgery. The expression levels of MMP-9, TIMP-1, alpha-smooth muscle actin (alpha-SMA) and fibronectin (FN) were examined by immunohistochemistry staining at each time point. RESULTS: In UUO rats, the disruption of renal tubular basement membrane (TBM) in PAS staining was found at day 3 after operation. At postoperative day 14 and 21, the TBM was observed to be thickened and wrinkled with partial and extensive disruption. On day 3 after UUO, the expressions of alpha-SMA and FN in tubulointerstitium were obviously increased. On day 7, some tubular epithelial cells also expressed alpha-SMA. In UUO rats, the strong positive expression of MMP-9 in renal tubulointerstitium was found at day 3 after operation and the expression peaked in tubulointerstitium at day 7, then decreased gradually. (4) In UUO rats, TIMP-1 expression in renal tubulointerstitium was increased progressively starting from day 3 to day 21. (5) The expression of MMP-9 in renal tubulointerstitium was significantly associated with the positive area of alpha-SMA and the disruption of TBM. CONCLUSION: The expression levels of MMP-9 and TIMP-1 relate closely to the disruption of TBM. TBM structural and functional integrity depends on many intricate interactions between MMP-9 and TIMP-1, which may play an important role in tubular epithelialmyofibroblast transdifferentiation.