PMID- 32934682
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 20
IP  - 5
DP  - 2020 Nov
TI  - Metformin attenuates renal interstitial fibrosis through upregulation of Deptor 
      in unilateral ureteral obstruction in rats.
PG  - 17
LID - 10.3892/etm.2020.9144 [doi]
LID - 17
AB  - Renal interstitial fibrosis (RIF) is a common pathological process that 
      accompanies chronic kidney disease (CKD) and that progresses to end-stage renal 
      failure (ESRD). Accumulating evidence has revealed that persistent mammalian 
      target of rapamycin (mTOR) activation in kidneys is closely associated with the 
      occurrence and progression of CKD. The DEP domain-containing mTOR interacting 
      protein (Deptor) is an endogenous negative regulator of mTOR. Metformin can 
      attenuate renal fibrosis in an animal model of diabetic nephropathy. Previous 
      studies demonstrated that metformin can attenuate renal fibrosis in several 
      models of CKD. However, the precise mechanisms of this effect are not well 
      understood. The present study aimed to examine the mechanism of action of 
      metformin on unilateral ureteral obstruction (UUO)-induced RIF in rats in vivo. 
      Sprague-Dawley rats were randomly divided into a sham-operated group, three UUO 
      groups examined at different time points (3, 7 and 14 days after UUO surgery), 
      and three metformin-treated groups, treated with three different concentrations 
      of metformin. The metformin-treated groups were administered metformin orally 
      every day for 14 consecutive days following surgery. The protein expression 
      levels of Deptor, alpha-smooth muscle actin (alpha-SMA), phosphorylated (p-)mTOR, 
      p-ribosomal protein S6 kinase (p-p70S6K) and CD68 were assessed. The present 
      results suggested that, following UUO, there was a significant reduction of 
      Deptor expression, and an increase in collagen deposition in the extracellular 
      matrix over time, accompanied by an increased expression of several proteins 
      including CD68, alpha-SMA, p-mTOR and p-p70S6K. Notably, metformin treatment reversed 
      these effects. In conclusion, the present results suggested that metformin 
      attenuated RIF of UUO rats, and the mechanism of action was found to be 
      associated with the increase in Deptor expression and inhibition of the 
      mTOR/p70S6K pathway in the kidneys of UUO rats.
CI  - Copyright: (c) Wang et al.
FAU - Wang, Yanxia
AU  - Wang Y
AD  - Department of Pharmacology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, 
      P.R. China.
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 
      Jiangsu 221000, P.R. China.
FAU - Li, Yong
AU  - Li Y
AD  - Department of Gastrointestinal Surgery, Xuzhou Central Hospital, Xuzhou, Jiangsu 
      221006, P.R. China.
FAU - Lu, Linghong
AU  - Lu L
AD  - Department of Pharmacology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, 
      P.R. China.
FAU - Peng, Yingxian
AU  - Peng Y
AD  - Department of Pharmacology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, 
      P.R. China.
FAU - Zhang, Shu
AU  - Zhang S
AD  - Department of Pharmacology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, 
      P.R. China.
FAU - Xia, Anzhou
AU  - Xia A
AD  - Department of Pharmacology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, 
      P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200826
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC7471900
OTO - NOTNLM
OT  - DEP domain-containing mTOR interacting protein
OT  - interstitial fibrosis
OT  - mTOR
OT  - metformin
OT  - unilateral ureteral obstruction
EDAT- 2020/09/17 06:00
MHDA- 2020/09/17 06:01
PMCR- 2020/08/26
CRDT- 2020/09/16 05:38
PHST- 2019/04/16 00:00 [received]
PHST- 2020/01/14 00:00 [accepted]
PHST- 2020/09/16 05:38 [entrez]
PHST- 2020/09/17 06:00 [pubmed]
PHST- 2020/09/17 06:01 [medline]
PHST- 2020/08/26 00:00 [pmc-release]
AID - ETM-0-0-09144 [pii]
AID - 10.3892/etm.2020.9144 [doi]
PST - ppublish
SO  - Exp Ther Med. 2020 Nov;20(5):17. doi: 10.3892/etm.2020.9144. Epub 2020 Aug 26.