PMID- 29934960
OWN - NLM
STAT- MEDLINE
DCOM- 20190730
LR  - 20190730
IS  - 1440-1797 (Electronic)
IS  - 1320-5358 (Linking)
VI  - 24
IP  - 4
DP  - 2019 Apr
TI  - Metformin inhibits TGF-beta 1-induced MCP-1 expression through BAMBI-mediated 
      suppression of MEK/ERK1/2 signalling.
PG  - 481-488
LID - 10.1111/nep.13430 [doi]
AB  - AIMS: Metformin is a biguanide derivative widely used for the treatment of type 2 
      diabetes mellitus. Recent evidence demonstrates that this anti-hyperglycaemic 
      drug exerts renal protective effects, yet the mechanisms remain poorly 
      understood. monocyte chemoattractant protein 1 (MCP-1) has been recognized as a 
      key mediator of renal fibrosis in chronic kidney diseases, including diabetic 
      nephropathy. This study aimed to investigate the effects of metformin on 
      transforming growth factor beta 1 (TGF-beta1)-induced MCP-1 expression and the 
      underlying mechanisms in rat renal tubular epithelial cells. METHODS: Rat renal 
      tubular epithelial cell line NRK-52E cells were stimulated with TGF-beta1 and/or 
      metformin. The messenger RNA (mRNA) of MCP-1 and bone morphogenetic protein and 
      activin membrane-bound inhibitor (BAMBI) was evaluated by real-time quantitative 
      polymerase chain reaction. MCP-1 protein was measured by enzyme linked 
      immunosorbent assay (ELISA). Total and phosphorylated extracellular 
      signal-regulated kinases 1/2 (ERK1/2) was evaluated by western blot. Down- and 
      upregulation of BAMBI were achieved by RNA interference targeting BAMBI and 
      lentiviral vector-mediated overexpression of the BAMBI gene, respectively. Cell 
      viability was analysed using Cell Counting Kit 8 (CCK-8) reagents. RESULTS: 
      Stimulation with TGF-beta1 resulted in the increased expression of MCP-1 and 
      decreased expression of BAMBI in NRK-52E cells. Metformin inhibited the 
      expression of MCP-1 in NRK-52E cells. Pretreatment with metformin suppressed 
      upregulation of MCP-1 and downregulation of BAMBI, as well as phosphorylation of 
      ERK1/2 induced by TGF-beta1. U0126, a specific inhibitor for mitogen-activated and 
      extracellular signal-regulated kinase kinases 1/2 (MEK-1/2), completely blocked 
      TGF-beta1-induced MCP-1 expression. Knockdown of the BAMBI gene promoted 
      phosphorylation of ERK1/2 and TGF-beta1-induced expression of MCP-1. Overexpression 
      of BAMBI inhibited phosphorylation of ERK1/2 and TGF-beta1-induced upregulation of 
      MCP-1. CONCLUSION: In rat renal tubular epithelial cells, metformin prevents 
      TGF-beta1-induced MCP-1 expression, in which BAMBI-mediated inhibition of MEK/ERK1/2 
      might be involved.
CI  - (c) 2018 Asian Pacific Society of Nephrology.
FAU - Liang, Diefei
AU  - Liang D
AD  - Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
AD  - Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Song, Zijiao
AU  - Song Z
AD  - Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
AD  - Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Liang, Weiwen
AU  - Liang W
AD  - Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Li, Yan
AU  - Li Y
AD  - Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
FAU - Liu, Shanying
AU  - Liu S
AD  - Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen 
      University, Guangzhou, China.
AD  - Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene 
      Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 
      China.
LA  - eng
GR  - Merck Serono Diabetes Foundation/
GR  - 81370847/National Natural Science Foundation of China/
PT  - Journal Article
PL  - Australia
TA  - Nephrology (Carlton)
JT  - Nephrology (Carlton, Vic.)
JID - 9615568
RN  - 0 (Bambi protein, rat)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Membrane Proteins)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
MH  - Animals
MH  - Cell Line
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Epithelial Cells/*drug effects/enzymology/pathology
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Fibrosis
MH  - Kidney Tubules/*drug effects/enzymology/pathology
MH  - Membrane Proteins/genetics/*metabolism
MH  - Metformin/*pharmacology
MH  - Mitogen-Activated Protein Kinase Kinases/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Signal Transduction/drug effects
MH  - Transforming Growth Factor beta1/*pharmacology
OTO - NOTNLM
OT  - BAMBI
OT  - MCP-1
OT  - TGF-beta1
OT  - metformin
OT  - renal tubular epithelial cell
EDAT- 2018/06/24 06:00
MHDA- 2019/07/31 06:00
CRDT- 2018/06/24 06:00
PHST- 2018/06/19 00:00 [accepted]
PHST- 2018/06/24 06:00 [pubmed]
PHST- 2019/07/31 06:00 [medline]
PHST- 2018/06/24 06:00 [entrez]
AID - 10.1111/nep.13430 [doi]
PST - ppublish
SO  - Nephrology (Carlton). 2019 Apr;24(4):481-488. doi: 10.1111/nep.13430.