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10.1038/srep05967

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suck abstract from ncbi


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pmid25095732
      Sci+Rep 2014 ; 4 (ä): 5967
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  • ?2AP mediated myofibroblast formation and the development of renal fibrosis in unilateral ureteral obstruction #MMPMID25095732
  • Kanno Y ; Kawashita E ; Kokado A ; Kuretake H ; Ikeda K ; Okada K ; Seishima M ; Ueshima S ; Matsuo O ; Matsuno H
  • Sci Rep 2014[Aug]; 4 (ä): 5967 PMID25095732 show ga
  • Renal fibrosis is the final common pathway of a wide variety of chronic kidney diseases. Myofibroblast formation via the differentiation of from tissue-resident fibroblasts and bone marrow-derived mesenchymal stem cells (MSCs), and epithelial-to-mesenchymal transition (EMT) is known to play a pivotal role in the development of renal fibrosis. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated the role of alpha 2-antiplasmin (?2AP) in myofibroblast formation and the development of renal fibrosis. We observed the development of renal fibrosis using unilateral ureteral obstruction (UUO). ?2AP had accumulated in the UUO-induced obstructed kidneys and ?2AP deficiency attenuated UUO-induced renal fibrosis in mice. The degree of myofibroblast formation in the obstructed kidneys of ?2AP(-/-) mice was less than that in ?2AP(+/+) mice. In vitro, ?2AP induced myofibroblast formation in renal tubular epithelial cells (RTECs), renal fibrosblasts, and bone marrow-derived mesenchymal stem cells (MSCs). ?2AP also induced the production of TGF-?, which is known to be a key regulator of myofibroblast formation and fibrosis. ?2AP-induced the TGF-? production was significantly reduced by SP600125, c-Jun N-terminal kinase (JNK) specific inhibitor. Our findings suggest that ?2AP induces myofibroblast formation in the obstructed kidneys, and mediates the development of renal fibrosis.
  • |Animals [MESH]
  • |Anthracenes/pharmacology [MESH]
  • |Cell Differentiation [MESH]
  • |Epithelial Cells/metabolism/pathology [MESH]
  • |Fibrosis [MESH]
  • |Gene Expression Regulation [MESH]
  • |Kidney/*metabolism/pathology [MESH]
  • |MAP Kinase Kinase 4/antagonists & inhibitors/genetics/metabolism [MESH]
  • |Male [MESH]
  • |Mesenchymal Stem Cells/metabolism/pathology [MESH]
  • |Mice [MESH]
  • |Mice, Knockout [MESH]
  • |Myofibroblasts/*metabolism/pathology [MESH]
  • |Primary Cell Culture [MESH]
  • |Protein Kinase Inhibitors/pharmacology [MESH]
  • |Renal Insufficiency/complications/*genetics/metabolism/pathology [MESH]
  • |Signal Transduction [MESH]
  • |Transforming Growth Factor beta/*genetics/metabolism [MESH]
  • |Ureter/metabolism/pathology [MESH]
  • |Ureteral Obstruction/complications/*genetics/metabolism/pathology [MESH]


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