Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/78439
Title: The hedgehog and Wnt/beta-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary fibrogenesis
Authors: Chen, X
Shi, CW
Cao, HH
Chen, L
Hou, JW
Xiang, Z 
Hu, KB
Han, XD
Issue Date: 2018
Publisher: Nature Publishing Group
Source: Cell death & disease, 29 May 2018, v. 9, 639 How to cite?
Journal: Cell death & disease 
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. Resident mesenchymal stem cells (LR-MSCs) can undergo phenotype conversion to myofibroblasts to augment extracellular matrix production, impairing function and contributing to pulmonary fibrosis. Hedgehog and Wnt signaling are developmental signal cascades that play an essential role in regulating embryogenesis and tissue homeostasis. Recently, it has been reported that both hedgehog and Wnt signaling play important roles in pulmonary fibrogenesis. Thus, the identification of specific target regulators may yield new strategy for pulmonary fibrosis therapies. In our work, we demonstrated the critical role of Gli1, Wnt7b, Wnt10a and Fzd10 in the process of pulmonary fibrogenesis in vitro and in vivo. Gli1 was induced in LR-MSCs following TGF-beta 1 treatment and fibrotic lung tissues. Inhibition of Gli1 suppressed myofibroblast differentiation of LRMSCs and pulmonary fibrosis, and decreased the expression of Wnt7b, Wnt10a and beta-catenin. Gli1 bound to and increased promoter activity of the Wnt7b and Wnt10a genes, and Wnt7b and Wnt10a were critical activators of Wnt/beta-catenin signaling. It was noteworthy that Fzd10 knockdown reduced Wnt7b and Wnt10a-induced activation of Wnt/beta-catenin signaling, which imply that Wnt7b and Wnt10a may be the ligands for Fzd10. Moreover, siRNA-mediated inhibition of Fzd10 prevented TGF-beta 1-induced myofibroblast differentiation of LR-MSCs in vitro and impaired bleomycin-induced pulmonary fibrosis. We conclude that hedgehog and Wnt/beta-catenin signaling play a critical role in promoting myofibroblast differentiation of LR-MSCs and development of pulmonary fibrosis. These findings elucidate a therapeutic approach to attenuate pulmonary fibrosis through targeted inhibition of Gli1 or Fzd10.
URI: http://hdl.handle.net/10397/78439
ISSN: 2041-4889
DOI: 10.1038/s41419-018-0692-9
Rights: © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the articles Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
The following publication Chen, X., Shi, C., Cao, H., Chen, L., Hou, J., Xiang, Z., . . . Han, X. (2018). The hedgehog and wnt/β-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary. Cell Death and Disease, 9(6), 639 is available at https://dx.doi.org/10.1038/s41419-018-0692-9
Appears in Collections:Journal/Magazine Article

Files in This Item:
File Description SizeFormat 
Chen_Hedgehog_Mediate_Myofibroblast.pdf3.17 MBAdobe PDFView/Open
Access
View full-text via PolyU eLinks SFX Query
Show full item record
PIRA download icon_1.1View/Download Contents

Page view(s)

9
Citations as of Dec 10, 2018

Download(s)

1
Citations as of Dec 10, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.