[Role of MMP-9 and TIMP-1 in renal tubular epithelial-myofibroblast transdifferentiation].
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.


CONCLUSIONS
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.
Xue
Hen
H
Department of Nephrology, West China Hosipital, Shichuan University, Chengdu 610041, China.
Chen
Liang
L
Fan
Jun-ming
JM
Li
Zi
Z
D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D004847:Epithelial Cells / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology*; D005353:Fibronectins / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051381:Rats; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
D000199:Actins; D005353:Fibronectins; D020780:Matrix Metalloproteinase 9; D019715:Tissue Inhibitor of Metalloproteinase-1; C498862:Acta2 protein, rat