Activation of AMPK Inhibits Galectin-3-induced Pulmonary Artery Smooth Muscle Cells Proliferation by Upregulating Hippo Signaling Effector YAP

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2021 Apr 2

PMID 33797701

Citations 15

Authors

Qianqian Zhang

Wenge Li

Yanting Zhu

Qingting Wang

Cui Zhai

Wenhua Shi

Wei Feng

Jian Wang

Xin Yan

Limin Chai

Yuqian Chen

Cong Li

Pengtao Liu

Manxiang Li

Affiliations

Soon will be listed here.

Abstract

Galectin-3(Gal-3) is an effective regulator in the pathological process of pulmonary arterial hypertension (PAH). However, the detailed mechanisms underlying Gal-3 contribution to PAH are not yet entirely clear. The aim of the present study was to explore these issues. Proliferation of rat pulmonary arterial smooth muscle cells (PASMCs) was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Small interfering RNA (siRNA) was applied to silence the expression of yes-associated protein (YAP) and Forkhead box M1 (FOXM1). The protein expression and phosphorylation were measured by immunoblotting. The subcellular location of YAP was determined using immunoblotting and immunofluorescence. Gal-3-stimulated PASMCs proliferation in a time- and dose-dependent manner, this was accompanied with, YAP upregulation, dephosphorylation, and nucleus translocation. Gal-3 further increased FOXM1 and cyclinD1 expression via YAP activation. Interfering YAP/FOXM1 axis suppressed Gal-3-induced PASMCs proliferation. Activation of AMPK also inhibited Gal-3-triggered cells proliferation by targeting YAP/FOXM1/cyclinD1 pathway. Gal-3 induced PASMCs proliferation by regulating YAP/FOXM1/cyclinD1 signaling cascade, and activation of AMPK targeted on this axis and suppressed Gal-3-stimulated PASMCs proliferation. Our study provides novel therapeutic targets for prevention and treatment of PAH.

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