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

IF 2.2 3区生物学 Q4 CELL BIOLOGY

Differentiation Pub Date : 2022-05-01 DOI:10.1016/j.diff.2022.03.004

Chaowen Shi , Xiang Chen , Wenna Yin , Zhaorui Sun , Jiwei Hou , Xiaodong Han

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引用次数: 0

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.

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Wnt8b通过激活肺纤维化过程中Wnt/β-catenin信号通路调控肺间充质干细胞的肌成纤维细胞分化

特发性肺纤维化(IPF)是一种慢性、进行性和致命的肺部疾病，其特征是干细胞分化和成纤维细胞增殖的增强变化。肺常驻间充质干细胞(LR-MSCs)是包括组织修复和炎症在内的病理生理过程的重要调节因子，有证据表明该细胞群在纤维化中也起着重要作用。我们之前的研究表明，Wnt/β-catenin信号在博莱霉素处理的小鼠肺部异常激活，并诱导LR-MSCs的肌成纤维细胞分化。然而，LR-MSCs与Wnt/β-catenin信号传导之间的潜在相关性仍然知之甚少。我们发现Wnt8b在肌成纤维细胞分化的LR-MSCs中高度表达。在体外，Wnt8b通过激活Wnt/β-catenin信号通路，促进LR-MSCs向肌成纤维细胞分化。此外，sirna介导的Wnt8b抑制可以阻止转化生长因子(TGF)-β1诱导的LR-MSCs的肌成纤维细胞分化，并改善肺纤维化病变。我们的研究在体外和体内发现了肺纤维化中的Wnt蛋白和Wnt/β-catenin信号，并强调了Wnt8b作为肺纤维化的潜在治疗靶点。此外，这些发现可能为IPF治疗策略的发展提供新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Differentiation 生物-发育生物学

CiteScore

4.10

自引率

3.40%

发文量

审稿时长

51 days

期刊介绍： Differentiation is a multidisciplinary journal dealing with topics relating to cell differentiation, development, cellular structure and function, and cancer. Differentiation of eukaryotes at the molecular level and the use of transgenic and targeted mutagenesis approaches to problems of differentiation are of particular interest to the journal. The journal will publish full-length articles containing original work in any of these areas. We will also publish reviews and commentaries on topics of current interest. The principal subject areas the journal covers are: • embryonic patterning and organogenesis • human development and congenital malformation • mechanisms of cell lineage commitment • tissue homeostasis and oncogenic transformation • establishment of cellular polarity • stem cell differentiation • cell reprogramming mechanisms • stability of the differentiated state • cell and tissue interactions in vivo and in vitro • signal transduction pathways in development and differentiation • carcinogenesis and cancer • mechanisms involved in cell growth and division especially relating to cancer • differentiation in regeneration and ageing • therapeutic applications of differentiation processes.