Metformin, an AMPK Activator, Inhibits Activation of FLSs but Promotes HAPLN1 Secretion

Molecular Therapy. Methods & Clinical Development
Yong ChenChanghong Xiao

Abstract

AMP-activated protein kinase (AMPK) is essential for maintaining energy balance and has a crucial role in various inflammatory pathways. In this study, AMPK levels positively correlated with many inflammatory indexes in rheumatoid arthritis (RA) patients, especially in the affected synovium. In RA sera, a positive correlation between phosphorylated (p-)AMPK-α1 levels and DAS28 (disease activity score 28) activity (r = 0.270, p < 0.0001) was found. Similarly, a positive correlation was observed between AMPK-α1 and tumor necrosis factor α (TNF-α) levels (r = 0.460, p = 0.0002). Differentially expressed genes between osteoarthritis (OA) and RA synovium from NCBI GEO profiles and our RNA sequencing data suggested activation of metabolic pathways specific to RA-fibroblast-like synoviocytes (FLSs). AMPK-α1 was highly expressed in the synovium of RA but not OA patients. An AMPK activator, metformin, inhibited FLS proliferation at higher but not lower concentrations, whereas the inhibitor dorsomorphin promoted the proliferation of RA-FLSs. Interestingly, both metformin and dorsomorphin inhibited the migration of RA-FLSs. After metformin treatment, expression of interleukin 6 (IL-6), TNF-α, and IL-1β were significantly downregulated in ...Continue Reading

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Citations

Aug 28, 2021·Life·Shenglan Wang, Yi Dai
Nov 2, 2021·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Tiancheng ZhangLizong Shen
Dec 9, 2021·The Korean Journal of Internal Medicine·Ji-Won KimSung-Hwan Park

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Datasets Mentioned

BETA
GSE55457

Methods Mentioned

BETA
ESR
targeted mutations
ELISA
enzyme-linked immunosorbent assay
Electrophoresis

Software Mentioned

GraphPad Prism
Compass

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