PMID- 37831352
OWN - NLM
STAT- Publisher
LR  - 20231013
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
DP  - 2023 Oct 13
TI  - Metformin modulates mitochondrial autophagy in renal tubular epithelial injury 
      induced by high glucose via the Keap1/Nrf2 pathway.
LID - 10.1007/s11010-023-04843-8 [doi]
AB  - The current study aimed to explore the role and underpinning molecular mechanisms 
      of metformin in renal cellular injury induced by high glucose levels. Male 
      C57BL/KsJ (db/db) and (db/m +) mice were utilized in this study. The experimental 
      group was administered 1 mg/mL of metformin through drinking water. Renal tissues 
      were harvested for hematoxylin and eosin (HE) staining, superoxide dismutase 
      (SOD) activity detection, biochemical indices analysis, Western blotting, and 
      qRT-PCR. HK-2 cells were utilized for Nrf2 siRNA transfection and to establish a 
      high level of glucose-induced cell models. Metformin was administered at a 
      concentration of 1 mmol/L in the experimental group. Cellular viability was 
      assessed using CCK-8, whereas acridine orange (AO) staining and LC3-mitotracker 
      co-localization staining were employed to evaluate autophagy. The expression of 
      Nrf2, P21, LC3, PTEN-induced putative kinase 1 (PINK1), translocase of outer 
      mitochondrial membrane 20 (TOMM20), and Kelch-like ECH-associated protein 1 
      (Keap1) were determined through Western blotting and qRT-PCR. Metformin mitigated 
      renal tissue inflammatory damage in diabetic mice, as indicated by upregulated 
      expression of Nrf2, PINK1, LC3, and TOMM20, and downregulated expression of Keap1 
      and P21. High level of glucose treatment in HK-2 cells resulted in decreased 
      autophagy, and reduced expression of Nrf2, PINK1, LC3, and TOMM20 alongside 
      elevated the expression of Keap1 and P21. Notably, metformin treatment partially 
      counteracted these effects. Nrf2 knockdown intensified these phenomena in the 
      high level of glucose-induced model. Protein-protein interaction network analysis 
      indicated that Nrf2 could regulate the majority autophagy-related proteins via 
      Keap1. Metformin modulates mitochondrial autophagy in high glucose-induced renal 
      tubular epithelial senescence via the Keap1/Nrf2 pathway.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Sun, Da
AU  - Sun D
AD  - Department of Nephrology, The First Hospital of China Medical University, No. 155 
      Nanjing Bei Street, Heping District, Shenyang, 110001, China.
FAU - Li, Huimin
AU  - Li H
AD  - Department of Nephrology, The Fourth Hospital of China Medical University, 
      Shenyang, 110000, China.
FAU - Du, Yinke
AU  - Du Y
AD  - Department of Nephrology, The First Hospital of China Medical University, No. 155 
      Nanjing Bei Street, Heping District, Shenyang, 110001, China.
FAU - Chen, Ying
AU  - Chen Y
AD  - Department of Nephrology, The First Hospital of China Medical University, No. 155 
      Nanjing Bei Street, Heping District, Shenyang, 110001, China.
FAU - Yao, Li
AU  - Yao L
AD  - Department of Nephrology, The First Hospital of China Medical University, No. 155 
      Nanjing Bei Street, Heping District, Shenyang, 110001, China.
FAU - Wang, Lining
AU  - Wang L
AD  - Department of Nephrology, The First Hospital of China Medical University, No. 155 
      Nanjing Bei Street, Heping District, Shenyang, 110001, China. lnwang56@163.com.
LA  - eng
GR  - NO.81370870/Projects from National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20231013
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
SB  - IM
OTO - NOTNLM
OT  - Autophagy
OT  - Diabetic nephropathy
OT  - Keap1-Nrf2
OT  - Metformin
OT  - Senescence
EDAT- 2023/10/13 12:42
MHDA- 2023/10/13 12:42
CRDT- 2023/10/13 11:16
PHST- 2023/06/28 00:00 [received]
PHST- 2023/08/24 00:00 [accepted]
PHST- 2023/10/13 12:42 [medline]
PHST- 2023/10/13 12:42 [pubmed]
PHST- 2023/10/13 11:16 [entrez]
AID - 10.1007/s11010-023-04843-8 [pii]
AID - 10.1007/s11010-023-04843-8 [doi]
PST - aheadofprint
SO  - Mol Cell Biochem. 2023 Oct 13. doi: 10.1007/s11010-023-04843-8.