PMID- 24791887
OWN - NLM
STAT- MEDLINE
DCOM- 20150406
LR  - 20171116
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 127
IP  - 9
DP  - 2014
TI  - Metformin inhibits nuclear factor-kappaB activation and inflammatory cytokines 
      expression induced by high glucose via adenosine monophosphate-activated protein 
      kinase activation in rat glomerular mesangial cells in vitro.
PG  - 1755-60
AB  - BACKGROUND: The renoprotective mechanisms of adenosine monophosphate 
      (AMP)-activated protein kinase (AMPK) agonist - metformin have not been stated 
      clearly. We hypothesized that metformin may ameliorate inflammation via AMPK 
      interaction with critical inflammatory cytokines. The aim of this study was to 
      observe the effects of metformin on expression of nuclear factor-kappaB (NF-kappaB), 
      monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 
      (ICAM-1) and transforming growth factor-beta 1 (TGF-beta1) induced by high glucose 
      (HG) in cultured rat glomerular mesangial cells (MCs). METHODS: MCs were cultured 
      in the medium with normal concentration glucose (group NG, 5.6 mmol/L), high 
      concentration glucose (group HG, 25 mmol/L) and different concentrations of 
      metformin (group M1, M2, M3). After 48-hour exposure, the supernatants and MCs 
      were collected. The expression of NF-kappaB, MCP-1, ICAM-1, and TGF-beta1 mRNA was 
      analyzed by real time polymerase chain reaction. Western blotting was used to 
      detect the expression of AMPK, phospho-Thr-172 AMPK (p-AMPK), NF-kappaB p65, MCP-1, 
      ICAM-1, and TGF-beta1 protein. RESULTS: After stimulated by HG, the expression of 
      NF-kappaB, MCP-1, ICAM-1, TGF-beta1 mRNA and protein of MCs in group HG increased 
      significantly compared with group NG (P < 0.05). Both genes and protein 
      expression of NF-kappaB, MCP-1, ICAM-1, TGF-beta1 of MCs induced by high glucose were 
      markedly reduced after metformin treatment in a dose-dependent manner (P < 0.05). 
      The expression of p-AMPK increased with the rising of metformin concentration, 
      presenting the opposite trend, while the level of total-AMPK protein was 
      unchanged with exposure to HG or metformin. Conlusion Metformin can suppress the 
      expression of NF-kappaB, MCP-1, ICAM-1 and TGF-beta1 of glomerular MCs induced by high 
      glucose via AMPK activation, which may partly contribute to its reno-protection.
FAU - Gu, Junfei
AU  - Gu J
AD  - Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui 
      Medical University, Hefei, Anhui 230001, China.
FAU - Ye, Shandong
AU  - Ye S
AD  - Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui 
      Medical University, Hefei, Anhui 230001, China. Email: ysd196406@163.com.
FAU - Wang, Shan
AU  - Wang S
AD  - Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui 
      Medical University, Hefei, Anhui 230001, China.
FAU - Sun, Wenjia
AU  - Sun W
AD  - Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui 
      Medical University, Hefei, Anhui 230001, China.
FAU - Hu, Yuanyuan
AU  - Hu Y
AD  - Department of Endocrinology, Anhui Provincial Hospital Affiliated to Anhui 
      Medical University, Hefei, Anhui 230001, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (NF-kappa B)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Glomerular Mesangium/cytology
MH  - Glucose/*pharmacology
MH  - Mesangial Cells/*drug effects/*metabolism
MH  - Metformin/*pharmacology
MH  - NF-kappa B/*metabolism
MH  - Rats
EDAT- 2014/05/06 06:00
MHDA- 2015/04/07 06:00
CRDT- 2014/05/06 06:00
PHST- 2014/05/06 06:00 [entrez]
PHST- 2014/05/06 06:00 [pubmed]
PHST- 2015/04/07 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2014;127(9):1755-60.