title: Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis.
abstract: Acute lung injury may lead to fibrogenesis. However, no treatment is currently available. This study was conducted to determine the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-1 and its receptor CXC chemokine receptor (CXCR)4 have been shown to participate in mobilizing MSCs. Adenovirus carrying the CXCR4 gene was used to transfect MSCs in order to increase the engraftment numbers of MSCs at injured sites. Histological examination data demonstrated that the engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis. The results showed that engraftment of MSCs almost differentiated into myofibroblasts, but rarely differentiated into lung epithelial cells. Additionally, it was demonstrated that activated canonical Wnt/β-catenin signaling in injured lung tissue regulated the myofibroblast differentiation of MSCs in vivo. The in vitro study results demonstrated that activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblast markers; however, this process was attenuated by Wnt antagonist DKK1. Therefore, the results demonstrated that the aberrant activation of Wnt signaling induces the myofibroblast differentiation of engrafted MSCs, thus contributing to pulmonary fibrosis following lung injury.
authors.affiliation: Immunology and Reproductive Biology Laboratory, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Zhaorui
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Immunology and Reproductive Biology Laboratory, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Immunology and Reproductive Biology Laboratory, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Chaowen
authors.initials: C
authors.lastname: Shi
authors.affiliation: Immunology and Reproductive Biology Laboratory, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Immunology and Reproductive Biology Laboratory, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Qian
authors.affiliation: Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors.forename: Shinan
authors.initials: S
authors.lastname: Nie
authors.affiliation: Immunology and Reproductive Biology Laboratory, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D006851:Hydrochloric Acid / Q000633:toxicity; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D058628:Myofibroblasts / Q000166:cytology* / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D006851:Hydrochloric Acid