Effect of fibrocystin on the proliferation of kidney cyst epithelial cells in autosomal recessive polycystic kidney disease
- VernacularTitle:Fibrocystin对常染色体隐性遗传多囊肾病囊肿细胞增殖的影响
- Author:
Jiyun YANG
;
Yang YANG
;
Ben ZHANG
- Publication Type:Journal Article
- Keywords:
Polycystic kidney,autosomal recessive;
RNA interference;
Epidermal growth factor;
Extracellular signal-regulated kinase;
PKHD1 gene
- From:
Chinese Journal of Nephrology
2008;24(5):349-355
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore whether the inhibited expression of fibrocystin by RNA interference can increase epidermal growth factor (EGF)-induced cell proliferation and its possible mechanism . Methods A stable PKHD1-silenced HEK 293 cell line was established . Cell proliferation rate, intracellular Ca2+ concentration and extracellular signal-reguhted kinase 1/2(ERK1/2) activity were assessed after treatment with EGF, verapamil and Bay K8644 . Results The proliferation rate of PKHD1-silenced HEK-293 cells was found to be significantly higher after EGF stimulation compared to the control HEK 293 cell (231 .5% vs 152 .8%, P＜0 .01) . PKHD1-silencing lowered the intracellular Ca2+ concentration and caused EGF-induced ERK1/2 overactivation in the cells(P＜0 .01 ) . When cells were treated with verapamil for 4 hours to lower the intracellular Ca2+ concentration, the cell proliferation rate was significantly increased after 20 ng EGF for 24 hours . The verapamil treatment increased the level of activated ERK1/2 in EGF-treated cells . An increase of intracellular Ca2 + in PKHD1-silenced ceils repressed the EGF-dependent ERK1/2 activation and the hyperproliferative response to EGF stimulation . Conclusions Inhibition of fibrocystin can cause EGF-induced excessive proliferation through decreasing intracellular Ca2+ resulting in EGF-induced ERK1/2 activation . The loss of fibrocystin may lead to abnormal proliferation in kidney epithelial cells and cyst formation in ARPKD through modulation of intracellular Ca2+ concentration .
