| First Author | Gui Y | Year | 2018 |
| Journal | J Biol Chem | Volume | 293 |
| Issue | 42 | Pages | 16364-16375 |
| PubMed ID | 30154246 | Mgi Jnum | J:292349 |
| Mgi Id | MGI:6268468 | Doi | 10.1074/jbc.RA118.004073 |
| Citation | Gui Y, et al. (2018) Yap/Taz mediates mTORC2-stimulated fibroblast activation and kidney fibrosis. J Biol Chem 293(42):16364-16375 |
| abstractText | Our previously published study demonstrated that mammalian target of rapamycin complex 2 (mTORC2) signaling mediates TGFbeta1-induced fibroblast activation. However, the underlying mechanisms for mTORC2 in stimulating fibroblast activation remain poorly understood. Here, we found that TGFbeta1 could stimulate mTORC2 and Yap/Taz activation in NRK-49F cells. Blocking either mTORC2 or Yap/Taz signaling diminished TGFbeta1-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. |
