PMID- 33530801
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20211204
IS  - 1473-2300 (Electronic)
IS  - 0300-0605 (Print)
IS  - 0300-0605 (Linking)
VI  - 49
IP  - 2
DP  - 2021 Feb
TI  - 1,25-(OH)(2)D(3) ameliorates renal interstitial fibrosis in UUO rats through the 
      AMPKalpha/mTOR pathway.
PG  - 300060520981360
LID - 10.1177/0300060520981360 [doi]
LID - 0300060520981360
AB  - OBJECTIVE: To investigate the effects of 1,25(OH)(2)D(3) on renal fibrosis 
      associated with the AMP-activated protein kinase (AMPK)alpha/mechanistic target of 
      rapamycin (mTOR) signalling pathway in a rat model of unilateral ureteral 
      obstruction (UUO). METHODS: A total of 54 male Sprague Dawley rats were randomly 
      divided into three groups: sham-operation group, UUO group, and UUO plus 
      calcitriol (3 ng/100 g) group. Renal tissue was excised for histological 
      examination by immunohistochemistry and Western blot, and for gene expression 
      analysis using real-time polymerase chain reaction. RESULTS: 1,25(OH)(2)D(3) 
      enhanced AMPKalpha levels, inhibited mTOR levels and slowed the development of 
      interstitial fibrosis in kidney tissue. Compared with the UUO plus calcitriol 
      group, UUO rats demonstrated more severe renal damage characterized by marked 
      tubular atrophy, interstitial fibrosis and significant induction of fibrogenic 
      transforming growth factor-beta1 and increased extra-cellular matrix proteins 
      (alpha-smooth muscle actin and collagen type III), and decreased E-cadherin. 
      CONCLUSION: Treatment with 1,25(OH)(2)D(3) altered the AMPKalpha/mTOR signalling 
      pathway to suppress excessive fibroblast activation observed in UUO rats. This 
      may serve as a novel mechanism to ameliorate renal dysfunction and fibrotic 
      lesions.
FAU - Tian, Shasha
AU  - Tian S
AUID- ORCID: 0000-0002-5306-410X
AD  - Department of Nephrology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, Shanxi, China.
FAU - Yang, Xiaopeng
AU  - Yang X
AD  - Department of Nephrology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, Shanxi, China.
FAU - Wang, Jianwu
AU  - Wang J
AD  - Department of Nephrology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, Shanxi, China.
FAU - Luo, Jing
AU  - Luo J
AD  - Department of Rheumatology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, Shanxi, China.
FAU - Guo, Hui
AU  - Guo H
AD  - Department of Nephrology, The Second Hospital of Shanxi Medical University, 
      Taiyuan, Shanxi, China.
AD  - Department of Nephrology, Shenzhen Baoan Shiyan People's Hospital, Shenzhen, 
      Guangdong, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Int Med Res
JT  - The Journal of international medical research
JID - 0346411
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics
MH  - Animals
MH  - Fibrosis
MH  - Kidney/pathology
MH  - *Kidney Diseases/drug therapy/etiology/pathology
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases
MH  - Transforming Growth Factor beta1/genetics
MH  - *Ureteral Obstruction
PMC - PMC7871069
OTO - NOTNLM
OT  - 1,25-(OH)2D3
OT  - AMPKalpha/mTOR
OT  - TGF-beta1
OT  - UUO
OT  - renal interstitial fibrosis
COIS- Declaration of conflicting interest: The authors declare that there is no 
      conflict of interest.
EDAT- 2021/02/04 06:00
MHDA- 2021/05/15 06:00
PMCR- 2021/02/02
CRDT- 2021/02/03 05:35
PHST- 2021/02/03 05:35 [entrez]
PHST- 2021/02/04 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2021/02/02 00:00 [pmc-release]
AID - 10.1177_0300060520981360 [pii]
AID - 10.1177/0300060520981360 [doi]
PST - ppublish
SO  - J Int Med Res. 2021 Feb;49(2):300060520981360. doi: 10.1177/0300060520981360.