A crosstalk between TGF-β/Smad3 and Wnt/β-catenin pathways promotes vascular smooth muscle cell proliferation

Cellular Signalling
Daniel DiRenzoK Craig Kent

Abstract

Endovascular interventions performed for atherosclerotic lesions trigger excessive vascular smooth muscle cell (SMC) proliferation leading to intimal hyperplasia. Our previous studies show that following endovascular injury, elevated TGF-β/Smad3 promotes SMC proliferation and intimal hyperplasia. Furthermore in cultured SMCs, elevated TGF-β/Smad3 increases the expression of several Wnt genes. Here we investigate a crosstalk between TGF-β/Smad3 and Wnt/β-catenin signaling and its role in SMC proliferation. To mimic TGF-β/Smad3 up-regulation in vivo, rat aortic SMCs were treated with Smad3-expressing adenovirus (AdSmad3) or AdGFP control followed by stimulation with TGF-β1 (or solvent). AdSmad3/TGF-β treatment up-regulated Wnt2b, Wnt4, Wnt5a, Wnt9a, and Wnt11 (confirmed by qRT-PCR and ELISA), and also increased β-catenin protein as detected by Western blotting. Blocking Wnt signaling using a Frizzled receptor inhibitor (Niclosamide) abolished TGF-β/Smad3-induced β-catenin stabilization. Increasing β-catenin through degradation inhibition (using SKL2001) or by adenoviral expression enhanced SMC proliferation. Furthermore, application of recombinant Wnt2b, Wnt4, Wnt5a, or Wnt9a, but not Wnt11, stabilized β-catenin and stimulated SM...Continue Reading

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Citations

Dec 8, 2017·Journal of Cellular Physiology·Yaling YangWeidong Tian
Apr 11, 2018·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Malini VisweswaranArun Dharmarajan
Mar 18, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Dario F Riascos-BernalNicholas E S Sibinga
Nov 20, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mathew Suji EapenSukhwinder Singh Sohal
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Jan 4, 2020·Experimental and Therapeutic Medicine·Jingsong CaoYi Wang
Apr 30, 2020·Signal Transduction and Targeted Therapy·Xuemin HeJian-Xing Ma
Aug 2, 2017·International Journal of Molecular Sciences·Ding-Yuan TianYun Wang
Aug 10, 2020·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Hualong BaiAlan Dardik
Jan 13, 2018·Journal of Ovarian Research·Daojuan WangYong Wang
Mar 29, 2021·Life Sciences·Yogamaya D Prabhu, Abilash Valsala Gopalakrishnan
May 20, 2021·Journal of Cardiovascular Pharmacology·Haozheng YuanXinsheng Han
Dec 2, 2021·The Journal of Clinical Investigation·Cyril DjariAnne-Marie Lefrançois-Martinez

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