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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 BMC+Cell+Biol
2016 ; 17
(1
): 21
Nephropedia Template TP
gab.com Text
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English Wikipedia
Matrix metalloproteinase 9 induces endothelial-mesenchymal transition via Notch
activation in human kidney glomerular endothelial cells
#MMPMID27130612
Zhao Y
; Qiao X
; Wang L
; Tan TK
; Zhao H
; Zhang Y
; Zhang J
; Rao P
; Cao Q
; Wang Y
; Wang Y
; Wang YM
; Lee VW
; Alexander SI
; Harris DC
; Zheng G
BMC Cell Biol
2016[Apr]; 17
(1
): 21
PMID27130612
show ga
BACKGROUND: Endothelial-mesenchymal transition (EndoMT) is a major source of
myofibroblast formation in kidney fibrosis. Our previous study showed a
profibrotic role for matrix metalloproteinase 9 (MMP-9) in kidney fibrosis via
induction of epithelial-mesenchymal transition (EMT). Inhibition of MMP-9
activity reduced kidney fibrosis in murine unilateral ureteral obstruction. This
study investigated whether MMP-9 also plays a role in EndoMT in human glomerular
endothelial cells. RESULTS: TGF-?1 (10 or 20 ng/ml) induced EndoMT in HKGECs as
shown by morphological changes. In addition, VE-cadherin and CD31 were
significantly downregulated, whereas ?-SMA, vimentin, and N-cadherin were
upregulated. RT-PCR revealed that Snail, a known inducer of EMT, was upregulated.
The MMP inhibitor GM6001 abrogated TGF-?1-induced EndoMT. Zymography indicated
that MMP-9 was also upregulated in TGF-?1-treated HKGECs. Recombinant MMP-9
(2 ?g/ml) induced EndoMT in HKGECs via Notch signaling, as evidenced by increased
formation of the Notch intracellular domain (NICD) and decreased Notch 1.
Inhibition of MMP-9 activity by its inhibitor showed a dose-dependent response in
preventing TGF-?1-induced ?-SMA and NICD in HKGECs, whereas inhibition of Notch
signaling by ?-secretase inhibitor (GSI) blocked rMMP-9-induced EndoMT.
CONCLUSIONS: Taken together, our results demonstrate that MMP-9 plays an
important role in TGF-?1-induced EndoMT via upregulation of Notch signaling in
HKGECs.
|Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism
[MESH]