PMID- 28585302
OWN - NLM
STAT- MEDLINE
DCOM- 20170919
LR  - 20220318
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Linking)
VI  - 242
IP  - 4
DP  - 2017 Aug
TI  - Rictor/mammalian target of rapamycin complex 2 promotes macrophage activation and 
      kidney fibrosis.
PG  - 488-499
LID - 10.1002/path.4921 [doi]
AB  - Mammalian target of rapamycin (mTOR) signalling controls many essential cellular 
      functions. However, the role of Rictor/mTOR complex 2 (mTORC2) in regulating 
      macrophage activation and kidney fibrosis remains largely unknown. We report here 
      that Rictor/mTORC2 was activated in macrophages from the fibrotic kidneys of 
      mice. Ablation of Rictor in macrophages reduced kidney fibrosis, inflammatory 
      cell accumulation, macrophage proliferation and polarization after unilateral 
      ureter obstruction or ischaemia/reperfusion injury. In bone marrow-derived 
      macrophages (BMMs), deletion of Rictor or blockade of protein kinase Calpha inhibited 
      cell migration. Additionally, deletion of Rictor or blockade of Akt abolished 
      interleukin-4-stimulated or transforming growth factor (TGF)-beta1-stimulated 
      macrophage M2 polarization. Furthermore, deletion of Rictor downregulated 
      TGF-beta1-stimulated upregulation of multiple profibrotic cytokines, including 
      platelet-derived growth factor, vascular endothelial growth factor and connective 
      tissue growth factor, in BMMs. Conditioned medium from TGF-beta1-pretreated 
      Rictor(-/-) macrophages stimulated fibroblast activation less efficiently than 
      that from TGF-beta1-pretreated Rictor(+/+) macrophages. These results demonstrate 
      that Rictor/mTORC2 signalling can promote macrophage activation and kidney 
      fibrosis. Targeting this signalling pathway in macrophages may shine light on 
      ways to protect against kidney fibrosis in patients with chronic kidney diseases. 
      Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
CI  - Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Ren, Jiafa
AU  - Ren J
AD  - Centre for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, PR China.
FAU - Li, Jianzhong
AU  - Li J
AD  - Centre for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, PR China.
FAU - Feng, Ye
AU  - Feng Y
AD  - Centre for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, PR China.
FAU - Shu, Bingyan
AU  - Shu B
AD  - Centre for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, PR China.
FAU - Gui, Yuan
AU  - Gui Y
AD  - Centre for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, PR China.
FAU - Wei, Wei
AU  - Wei W
AD  - Centre for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, PR China.
FAU - He, Weichun
AU  - He W
AD  - Centre for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, PR China.
FAU - Yang, Junwei
AU  - Yang J
AD  - Centre for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, PR China.
FAU - Dai, Chunsun
AU  - Dai C
AUID- ORCID: 0000-0001-7616-2469
AD  - Centre for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, 
      Nanjing, Jiangsu, PR China.
LA  - eng
PT  - Journal Article
DEP - 20170712
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (rictor protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/metabolism/*physiology
MH  - Cell Movement/physiology
MH  - Cell Polarity/physiology
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Disease Models, Animal
MH  - Fibrosis
MH  - Kidney/metabolism/*pathology
MH  - Macrophage Activation/*physiology
MH  - Macrophages/metabolism
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 2
MH  - Mice, Inbred C57BL
MH  - Multiprotein Complexes/*physiology
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/*physiology
MH  - Up-Regulation/physiology
OTO - NOTNLM
OT  - Rictor/mTORC2
OT  - kidney fibrosis
OT  - macrophage
EDAT- 2017/06/07 06:00
MHDA- 2017/09/20 06:00
CRDT- 2017/06/07 06:00
PHST- 2017/01/17 00:00 [received]
PHST- 2017/05/01 00:00 [revised]
PHST- 2017/05/24 00:00 [accepted]
PHST- 2017/06/07 06:00 [pubmed]
PHST- 2017/09/20 06:00 [medline]
PHST- 2017/06/07 06:00 [entrez]
AID - 10.1002/path.4921 [doi]
PST - ppublish
SO  - J Pathol. 2017 Aug;242(4):488-499. doi: 10.1002/path.4921. Epub 2017 Jul 12.