Inhibition of Wnt/β-catenin signaling promotes epithelial differentiation of mesenchymal stem cells and repairs bleomycin-induced lung injury
| Autor: | Can Ni, Zou Xiang, Cong Wang, Huiming Zhu, Weiping Qian, Yuanyuan Ge, Zhaowen Luo, Zhaorui Sun, Xiaodong Han |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Pathology
medicine.medical_specialty Epithelial-Mesenchymal Transition Physiology Apoptosis Bone Marrow Cells Lung injury Biology Cell Line Idiopathic pulmonary fibrosis Bleomycin Mice Pulmonary fibrosis medicine Animals Myofibroblasts Wnt Signaling Pathway beta Catenin Cell Proliferation Lung Mesenchymal stem cell Wnt signaling pathway LRP5 Cell Differentiation Epithelial Cells Mesenchymal Stem Cells Cell Biology 3T3 Cells Lung Injury medicine.disease Coculture Techniques Idiopathic Pulmonary Fibrosis Mice Inbred C57BL Pulmonary Alveoli Wnt Proteins medicine.anatomical_structure Cancer research Signal transduction Heterocyclic Compounds 3-Ring |
| Zdroj: | American journal of physiology. Cell physiology. 307(3) |
| ISSN: | 1522-1563 |
| Popis: | Idiopathic pulmonary fibrosis is a progressive lung disorder of unknown etiology. Previous studies have shown that aberrant activation of the Wnt/β-catenin signaling cascade occurs in lungs of patients with idiopathic pulmonary fibrosis. Given the important roles of the Wnt/β-catenin signaling pathway in the development of pulmonary fibrosis, we targeted this pathway for the intervention of pulmonary fibrosis with XAV939, a small molecule that specifically inhibits Tankyrase 1/2, eventually leading to the degradation of β-catenin and suppression of the Wnt/β-catenin signaling pathway. Our results demonstrated that XAV939 significantly inhibited the activation of Wnt/β-catenin signaling and attenuated bleomycin-induced lung fibrosis in mice, and thus improved the survival of mice with lung injury. Interestingly, previous investigations have confirmed that endogenous and exogenous mesenchymal stem cells could be recruited to the injured lung, although the exact effects of these cells are debatable. To determine the effect of Wnt/β-catenin signaling in the epithelial differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs), we established a coculture system that contains BM-MSCs and alveolar type II epithelial cells. The in vitro experiments demonstrated that XAV939 could promote the differentiation of BM-MSCs into an epithelium-like phenotype in the coculture system. We also found that XAV939 could inhibit the proliferation and myofibroblast differentiation of NIH/3T3 fibroblasts. This work supports that inhibition of the Wnt/β-catenin signaling pathway may be exploited for the treatment of idiopathic pulmonary fibrosis for which effective treatment strategies are still lacking. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|