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10.1186/s12860-016-0101-0

http://scihub22266oqcxt.onion/10.1186/s12860-016-0101-0
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suck abstract from ncbi


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pmid27130612      BMC+Cell+Biol 2016 ; 17 (ä): ä
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  • 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 VWS; Alexander SI; Harris DCH; Zheng G
  • BMC Cell Biol 2016[]; 17 (ä): ä PMID27130612show 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.
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