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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Transl+Res
2016 ; 8
(2
): 662-9
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Glioma-associated oncogene homolog 1 promotes epithelial-mesenchymal transition
in human renal tubular epithelial cell
#MMPMID27158358
Ding H
; Xu Y
; Gao D
; Wang L
Am J Transl Res
2016[]; 8
(2
): 662-9
PMID27158358
show ga
Sonic hedgehog (Shh) signaling critically regulates embryogenesis and tissue
homeostasis. Here, we investigated the role of Shh signaling in mediating
epithelial-mesenchymal transition (EMT) in human renal tubular epithelial cells
HKC-8. Our RT-PCR assays demonstrated that TGF-?1 induced time-dependent changes
in the mRNA transcript levels of Shh, with a steady rise from one hour post
TGF-?1 treatment and a peak at four hours post TGF-?1 treatment. Furthermore,
TGF-?1 induced a time-dependent increase in the mRNA transcript levels of Gli1.
Pre-treatment with 2 or 5 µM cyclopamine significantly attenuated TGF-?1-induced
rise in the mRNA transcript levels of Gli1, but failed to attenuate
TGF-?1-induced rise in Shh mRNA transcript levels. Additionally, immunoblotting
assays and immunofluorescence staining demonstrated that inhibition of Shh
signaling by cyclopamine significantly attenuated TGF-?1-induced increase in the
mRNA transcript levels of ?-SMA, collagen I, and fibronectin. Gli1 overexpression
induced Snail1 expression. Moreover, Gli(-/-) mice that had undergone unilateral
ureteral obstruction for seven days showed significant reduction in the mRNA
transcript levels of Snail1 compared to the wildtype controls. In conclusion, the
current study provides novel insight into the regulation of EMT by the Shh/Gli1
signaling pathway, suggesting a critical role of Shh/Gli1 signaling in EMT of
human renal tubular epithelial cells.