Activation of AMPK inhibits TGF-?1-induced airway smooth muscle cells proliferation and its potential mechanisms.

ABSTRACT: The aims of the present study were to examine signaling mechanisms underlying transforming growth factor ?1 (TGF-?1)-induced airway smooth muscle cells (ASMCs) proliferation and to determine the effect of adenosine monophosphate-activated protein kinase (AMPK) activation on TGF-?1-induced ASMCs proliferation and its potential mechanisms. TGF-?1 reduced microRNA-206 (miR-206) level by activating Smad2/3, and this in turn up-regulated histone deacetylase 4 (HDAC4) and consequently increased cyclin D1 protein leading to ASMCs proliferation. Prior incubation of ASMCs with metformin induced AMPK activation and blocked TGF-?1-induced cell proliferation. Activation of AMPK slightly attenuated TGF-?1-induced miR-206 suppression, but dramatically suppressed TGF-?1-caused HDAC4 up-expression and significantly increased HDAC4 phosphorylation finally leading to reduction of up-regulated cyclin D1 protein expression. Our study suggests that activation of AMPK modulates miR-206/HDAC4/cyclin D1 signaling pathway, particularly targeting on HDAC4, to suppress ASMCs proliferation and therefore has a potential value in the prevention and treatment of asthma by alleviating airway remodeling.

SUBMITTER: Pan Y 

PROVIDER: S-EPMC5827654 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature