[Effects of hepatocyte growth factor on IL-1alpha triggered tubular epithelial-myofibroblast transdifferentiation and fibronectin secretion in vitro].
OBJECTIVE
To observe the effects of hepatocyte growth factor (HGF) on tubular epithelial-myofibroblast transdifferentiation (TEMT) triggered by IL-1alpha and the fibronectin secretion of TEMT.


METHODS
The normal rat kidney tubular epithelial cell line (NRK52E) was cultured for six days on plastic or collagen type I-coated plates in the presence or absence of HGF or IL-1alpha. The morphology of transdifferentiation tubular cells was observed by scanning electron microscopy (SEM) and phase-contrast microscopy. The number of alpha-SMA+ cells, the percentage of alpha-SMA+ cells and the mean channel fluorescence (MCF) were assessed by immunohistochemistry and flowcytometry. The level of fibronectin in supernatant was measured by ELISA.


RESULTS
The NRK52E cells triggered by IL-1alpha became fibroblast-like morphologically, and strong alpha-SMA immunostaining of those cells was seen. The level of FN in the culture supernatant, the percentage of alpha-SMA+ cells and the MCF of cells triggered by IL-1alpha were obviously higher than those of blank control group (P<0.05). In the groups with IL-1alpha and different doses of HGF, the transdifferentiation of NRK52E cells was inhibited. With the increase of HGF dose, the percentage of alpha-SMA+ cells and the level of FN showed a tendency to decrease. There was no significant difference between the groups treated with only HGF at different dose levels and the blank control group (P>0.05).


CONCLUSIONS
IL-1alpha can induce tubular epithelial cell to transdifferentiate to myofibroblast and increase the secretion of FN. These results suggest that TEMT may play an important role in the pathogenesis of renal fibrosis. HGF could block the transdifferentiation of tubular epithelial cell and inhibit the secretion of FN. These would provide a novel therapeutic strategy for the treatment of renal interstitial fibrosis and end stage renal disease.
Liu
Xin-ying
XY
Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China.
Luo
Hai
H
Wang
Mi
M
Chen
Hui-zhen
HZ
Su
Bai-hai
BH
Li
Zi
Z
Xu
Guo-zhang
GZ
Fan
Jun-ming
JM
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007684:Kidney Tubules / Q000166:cytology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D051381:Rats
D000199:Actins; D005353:Fibronectins; D017228:Hepatocyte Growth Factor; D007375:Interleukin-1; C498862:Acta2 protein, rat