Wnt8b regulates myofibroblast differentiation of lung-resident mesenchymal stem cells via the activation of Wnt/β-catenin signaling in pulmonary fibrogenesis.

Abstract	Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease that is characterized by enhanced changes in stem cell differentiation and fibroblast proliferation. Lung resident mesenchymal stem cells (LR-MSCs) are important regulators of pathophysiological processes including tissue repair and inflammation, and evidence suggests that this cell population also plays an essential role in fibrosis. Our previous study demonstrated that Wnt/β-catenin signaling is aberrantly activated in the lungs of bleomycin-treated mice and induces myofibroblast differentiation of LR-MSCs. However, the underlying correlation between LR-MSCs and the Wnt/β-catenin signaling remains poorly understood. We found that Wnt8b was highly expressed by LR-MSCs undergoing myofibroblast differentiation. In vitro, Wnt8b promoted LR-MSCs differentiate into myofibroblasts via activating Wnt/β-catenin signaling. Moreover, siRNA-mediated inhibition of Wnt8b prevented Transforming growth factor (TGF)-β1-induced myofibroblast differentiation of LR-MSCs in vitro and ameliorated pulmonary fibrotic lesions. Our study identified Wnt proteins and Wnt/β-catenin signaling in pulmonary fibrosis in vitro and in vivo, and highlighted Wnt8b as a potential therapeutic target in pulmonary fibrosis. Moreover, these finding might provide a new perspective in the development of treatment strategies for IPF.
Authors	Chaowen Shi, Xiang Chen, Wenna Yin, Zhaorui Sun, Jiwei Hou, Xiaodong Han
Journal	Differentiation; research in biological diversity (Differentiation) 2022 May-Jun Vol. 125 Pg. 35-44 ISSN: 1432-0436 [Electronic] England
PMID	35487030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Chemical References	Wnt Proteins Wnt8b protein, mouse beta Catenin
Topics	Animals Cell Differentiation (genetics) Idiopathic Pulmonary Fibrosis (metabolism) Lung Mesenchymal Stem Cells Mice Mice, Inbred C57BL Myofibroblasts (pathology) Wnt Proteins (metabolism) beta Catenin (genetics, metabolism)

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