PMID- 36186658
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221004
IS  - 1687-8337 (Print)
IS  - 1687-8345 (Electronic)
IS  - 1687-8337 (Linking)
VI  - 2022
DP  - 2022
TI  - Blocking REDD1/TXNIP Complex Ameliorates HG-Induced Renal Tubular Epithelial Cell 
      Apoptosis and EMT through Repressing Oxidative Stress.
PG  - 6073911
LID - 10.1155/2022/6073911 [doi]
LID - 6073911
AB  - Diabetic nephropathy (DN) has become the most common secondary kidney disease 
      causing end-stage renal disease (ESRD). Nevertheless, the underlying mechanisms 
      responsible for DN remain largely unknown. Regulated in development and DNA 
      damage response 1 (REDD1) is a prooxidative molecule known to contribute to 
      diabetes mellitus and its complications. However, it has not been previously 
      examined whether and how REDD1 can further drive renal tubular epithelial cell 
      (RTEC) apoptosis and epithelial-to-mesenchymal transition in DN. The expression 
      of REDD1 was elevated in the kidneys of DN patients and diabetic mice in this 
      study. By generating the DN model in REDD1 knockout mice, we demonstrated that 
      REDD1 deficiency significantly improved apoptosis and EMT in diabetic mice. In 
      vitro experiments showed that REDD1 generation was induced by high glucose (HG) 
      in HK-2 cells. Similarly, the transfection of REDD1 siRNA plasmid also suppressed 
      HG-induced apoptosis and EMT. Furthermore, we discovered that the inhibition of 
      REDD1 suppressed the expression of Nox4-induced HG and reactive oxygen species 
      (ROS) synthesis in HK-2 cells. In addition, HG could induce endogenous REDD1 and 
      TXNIP to form a powerful complex. In summary, our findings demonstrate that 
      blocking the REDD1/TXNIP complex can prevent HG-induced apoptosis and EMT by 
      inhibiting ROS production, highlighting REDD1 as a valuable therapeutic priority 
      site for DN.
CI  - Copyright (c) 2022 Lin Mu et al.
FAU - Mu, Lin
AU  - Mu L
AUID- ORCID: 0000-0003-2814-253X
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang 050000, China.
AD  - Hebei Key Laboratory of Kidney Disease, Shijiazhuang 050000, China.
AD  - Department of Nephrology, Second Hospital of Hebei Medical University, 
      Shijiazhuang 050000, China.
FAU - Chen, Nan
AU  - Chen N
AUID- ORCID: 0000-0002-7408-4169
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang 050000, China.
FAU - Chen, Yakun
AU  - Chen Y
AUID- ORCID: 0000-0001-5590-6545
AD  - Department of Nephrology, Second Hospital of Hebei Medical University, 
      Shijiazhuang 050000, China.
FAU - Yang, Zhifen
AU  - Yang Z
AUID- ORCID: 0000-0003-1464-0140
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang 050000, China.
FAU - Zhou, Huandi
AU  - Zhou H
AUID- ORCID: 0000-0002-2617-6157
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang 050000, China.
FAU - Song, Shan
AU  - Song S
AUID- ORCID: 0000-0002-2841-2213
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang 050000, China.
AD  - Hebei Key Laboratory of Kidney Disease, Shijiazhuang 050000, China.
FAU - Shi, Yonghong
AU  - Shi Y
AUID- ORCID: 0000-0002-8920-6966
AD  - Department of Pathology, Hebei Medical University, Shijiazhuang 050000, China.
AD  - Hebei Key Laboratory of Kidney Disease, Shijiazhuang 050000, China.
LA  - eng
PT  - Journal Article
DEP - 20220921
PL  - Egypt
TA  - Int J Endocrinol
JT  - International journal of endocrinology
JID - 101516376
PMC - PMC9519289
COIS- The authors declare no conflicts of interest.
EDAT- 2022/10/04 06:00
MHDA- 2022/10/04 06:01
PMCR- 2022/09/21
CRDT- 2022/10/03 04:37
PHST- 2022/03/21 00:00 [received]
PHST- 2022/08/14 00:00 [accepted]
PHST- 2022/10/03 04:37 [entrez]
PHST- 2022/10/04 06:00 [pubmed]
PHST- 2022/10/04 06:01 [medline]
PHST- 2022/09/21 00:00 [pmc-release]
AID - 10.1155/2022/6073911 [doi]
PST - epublish
SO  - Int J Endocrinol. 2022 Sep 21;2022:6073911. doi: 10.1155/2022/6073911. 
      eCollection 2022.