PMID- 34095318
OWN - NLM
STAT- MEDLINE
DCOM- 20211210
LR  - 20240226
IS  - 2314-6753 (Electronic)
IS  - 2314-6745 (Print)
VI  - 2021
DP  - 2021
TI  - Tacrolimus Protects Podocytes from Apoptosis via Downregulation of TRPC6 in 
      Diabetic Nephropathy.
PG  - 8832114
LID - 10.1155/2021/8832114 [doi]
LID - 8832114
AB  - Podocyte injury plays an important role in diabetic nephropathy (DN), and 
      apoptosis is one of its mechanisms. The transient receptor potential channel 6 
      (TRPC6) is expressed in podocytes and mediates podocyte injury induced by high 
      glucose levels. Tacrolimus is a novel immunosuppressive agent that is reported to 
      play an important role in podocyte protection. The purpose of this study was to 
      investigate the potential mechanism of podocyte protection by tacrolimus in a 
      type 2 diabetic mellitus (T2DM) rat model and in immortalized mouse podocytes 
      (MPC5). Transmission electron microcopy was used to evaluate renal injury 
      morphology. After treatment with FK506, we measured 24-hour urinary 
      albumin-to-creatinine ratios and creatinine clearance rates as well as major 
      biochemical parameters such as glucose, insulin, serum creatinine, urea nitrogen, 
      total cholesterol, triglycerides, alanine transaminase, and aspartate 
      aminotransferase. Nephrin and TRPC6 protein expression and podocyte apoptotic 
      rates in vivo and in vitro were measured using immunohistochemical staining, 
      TUNEL assays, and flow cytometry, respectively. Western blot was used to measure 
      expression of cleaved-caspase-3 and bax/bcl-2. Exposed to high glucose (HG), DM 
      rats exhibited disrupted biochemical conditions and impaired podocyte structure. 
      Decreased expression of nephrin and increased expression of TRPC6, 
      cleaved-caspase-3, and bax/bcl-2 ratios were found in podocytes, along with 
      higher apoptotic percentage, while tacrolimus intervention counteracted the 
      effect of HG on podocytes. Our results suggest that tacrolimus protects podocytes 
      during the progression of type 2 diabetic nephropathy, possibly ameliorating 
      podocyte apoptosis by downregulating the expression of TRPC6.
CI  - Copyright (c) 2021 Ruixia Ma et al.
FAU - Ma, Ruixia
AU  - Ma R
AUID- ORCID: 0000-0002-5492-2575
AD  - Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, China.
FAU - Wang, Ying
AU  - Wang Y
AUID- ORCID: 0000-0002-4847-2539
AD  - Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, China.
FAU - Xu, Yan
AU  - Xu Y
AD  - Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, China.
FAU - Wang, Rui
AU  - Wang R
AD  - Department of Intensive Care Unit, Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China.
FAU - Wang, Xianghua
AU  - Wang X
AD  - Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, China.
FAU - Yu, Ning
AU  - Yu N
AD  - Department of Ultrasound, Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, China.
FAU - Li, Minghui
AU  - Li M
AD  - Department of Emergency, Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, China.
FAU - Zhou, Yan
AU  - Zhou Y
AD  - Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, 
      Shandong, China.
LA  - eng
PT  - Journal Article
DEP - 20210520
PL  - England
TA  - J Diabetes Res
JT  - Journal of diabetes research
JID - 101605237
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (TRPC6 Cation Channel)
RN  - 0 (Trpc6 protein, mouse)
RN  - 0 (Trpc6 protein, rat)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Cell Line
MH  - Diabetic Nephropathies/*drug therapy/genetics/metabolism/pathology
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Male
MH  - Mice
MH  - Podocytes/*drug effects/metabolism/ultrastructure
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - TRPC Cation Channels/genetics/*metabolism
MH  - TRPC6 Cation Channel/genetics/*metabolism
MH  - Tacrolimus/*pharmacology
MH  - Rats
PMC - PMC8163546
COIS- All authors declare no financial competing interests.
EDAT- 2021/06/08 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/05/20
CRDT- 2021/06/07 06:05
PHST- 2020/09/13 00:00 [received]
PHST- 2021/04/18 00:00 [revised]
PHST- 2021/04/24 00:00 [accepted]
PHST- 2021/06/07 06:05 [entrez]
PHST- 2021/06/08 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/05/20 00:00 [pmc-release]
AID - 10.1155/2021/8832114 [doi]
PST - epublish
SO  - J Diabetes Res. 2021 May 20;2021:8832114. doi: 10.1155/2021/8832114. eCollection 
      2021.