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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 (1 ): 21
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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 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]
  • |Dipeptides/pharmacology [MESH]
  • |Endothelial Cells/drug effects/*metabolism [MESH]
  • |Humans [MESH]
  • |Kidney Glomerulus/*cytology [MESH]
  • |Matrix Metalloproteinase 9/*metabolism [MESH]
  • |Matrix Metalloproteinase Inhibitors/pharmacology [MESH]
  • |Mesoderm/*cytology/drug effects [MESH]
  • |Receptors, Notch/*metabolism [MESH]
  • |Recombinant Proteins/pharmacology [MESH]
  • |Signal Transduction/drug effects [MESH]


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