| First Author | Li J | Year | 2015 |
| Journal | Kidney Int | Volume | 88 |
| Issue | 3 | Pages | 515-27 |
| PubMed ID | 25970154 | Mgi Jnum | J:315366 |
| Mgi Id | MGI:6830261 | Doi | 10.1038/ki.2015.119 |
| Citation | Li J, et al. (2015) Rictor/mTORC2 signaling mediates TGFbeta1-induced fibroblast activation and kidney fibrosis. Kidney Int 88(3):515-27 |
| abstractText | The mammalian target of rapamycin (mTOR) was recently identified in two structurally distinct multiprotein complexes: mTORC1 and mTORC2. Previously, we found that Rictor/mTORC2 protects against cisplatin-induced acute kidney injury, but the role and mechanisms for Rictor/mTORC2 in TGFbeta1-induced fibroblast activation and kidney fibrosis remains unknown. To study this, we initially treated NRK-49F cells with TGFbeta1 and found that TGFbeta1 could activate Rictor/mTORC2 signaling in cultured cells. Blocking Rictor/mTORC2 signaling with Rictor or Akt1 small interfering RNAs markedly inhibited TGFbeta1-induced fibronection and alpha-smooth muscle actin expression. Ensuing western blotting or immunostaining results showed that Rictor/mTORC2 signaling was activated in kidney interstitial myofibroblasts from mice with unilateral ureteral obstruction. Next, a mouse model with fibroblast-specific deletion of Rictor was generated. These knockout mice were normal at birth and had no obvious kidney dysfunction or kidney morphological abnormality within 2 months of birth. Compared with control littermates, the kidneys of Rictor knockout mice developed less interstitial extracellular matrix deposition and inflammatory cell infiltration at 1 or 2 weeks after ureteral obstruction. Thus our study suggests that Rictor/mTORC2 signaling activation mediates TGFbeta1-induced fibroblast activation and contributes to the development of kidney fibrosis. This may provide a therapeutic target for chronic kidney diseases. |
