Jianzhong Li;Jiafa Ren;Xin Liu;雷 江;Weichun He;Weiping Yuan;Junwei Yang;Chunsun Dai
Nanjing Medical University;China Association for Science and Technology;Chinese Academy of Medical Sciences
发表时间:2015-9-3
期 刊:Kidney International
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=84940789259&partnerID=8YFLogxK
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 TGFβ1-induced fibroblast activation and kidney fibrosis remains unknown. To study this, we initially treated NRK-49F cells with TGFβ1 and found that TGFβ1 could activate Rictor/mTORC2 signaling in cultured cells. Blocking Rictor/mTORC2 signaling with Rictor or Akt1 small interfering RNAs markedly inhibited TGFβ1-induced fibronection and α-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 TGFβ1-induced fibroblast activation and contributes to the development of kidney fibrosis. This may provide a therapeutic target for chronic kidney diseases.
医学与生命科学
Scopus度量
年份 | CiteScore | SJR | SNIP |
---|---|---|---|
1996 | |||
1997 | |||
1998 | |||
1999 | 1.724 | 1.928 | |
2000 | 2.03 | 1.634 | |
2001 | 2.169 | 1.84 | |
2002 | 2.219 | 1.845 | |
2003 | 2.364 | 1.809 | |
2004 | 2.085 | 1.727 | |
2005 | 2.189 | 1.817 | |
2006 | 2.183 | 1.701 | |
2007 | 2.325 | 1.757 | |
2008 | 2.527 | 1.864 | |
2009 | 2.42 | 2.076 | |
2010 | 2.461 | 1.888 | |
2011 | 10.5 | 2.559 | 1.995 |
2012 | 11.5 | 3.276 | 2.198 |
2013 | 13.7 | 3.542 | 2.492 |
2014 | 14.8 | 3.348 | 2.605 |
2015 | 13.4 | 3.174 | 2.369 |
2016 | 13.1 | 3.058 | 2.439 |
2017 | 13.2 | 3.238 | 2.431 |
2018 | 12.8 | 3.331 | 2.502 |
2019 | 12.8 | 3.425 | 2.655 |
2020 | 12.8 |
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