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RSS FeedsYap/Taz mediates mTORC2-stimulated fibroblast activation and kidney fibrosis [Cell Biology] (Journal of Biological Chemistry)

 
 

21 october 2018 10:00:16

 
Yap/Taz mediates mTORC2-stimulated fibroblast activation and kidney fibrosis [Cell Biology] (Journal of Biological Chemistry)
 


Our previously published study demonstrated that mammalian target of rapamycin complex 2 (mTORC2) signaling mediates TGF?1-induced fibroblast activation. However, the underlying mechanisms for mTORC2 in stimulating fibroblast activation remain poorly understood. Here, we found that TGF?1 could stimulate mTORC2 and Yap/Taz activation in NRK-49F cells. Blocking either mTORC2 or Yap/Taz signaling diminished TGF?1-induced fibroblast activation. In addition, blockade of mTORC2 could down-regulate the expression of Yap/Taz, connective tissue growth factor (CTGF), and ankyrin repeat domain 1 (ANKRD1). Overexpression of constitutively active Taz (Taz-S89A) could restore fibroblast activation suppressed by PP242, an mTOR kinase inhibitor in NRK-49F cells. In mouse kidneys with unilateral ureter obstructive (UUO) nephropathy, both mTORC2 and Yap/Taz were activated in the interstitial myofibroblasts. Ablation of Rictor in fibroblasts/pericytes or blockade of mTOR signaling with PP242 attenuated Yap/Taz activation and UUO nephropathy in mice. Together, this study uncovers that targeting mTORC2 retards fibroblast activation and kidney fibrosis through suppressing Yap/Taz activation.


 
113 viewsCategory: Biochemistry
 
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