Wnt signaling regulates the differentiation of bone marrowmesenchymal stem cells after lung injury
Stromal cell-derived factor-I (SDF-1) and its receptor CXCR4 has been shown to participate in mobilizing bone marrow-derived mesenchymal stem cells (MSCs).Westudied the effects ofMSCs in a model of HCl-indueed acute lung injury in SD rats by modulating the SDF-(1)/CXCR4 axis.After intranasal instillation of HCl,SDF-1 levels in serum and lung tissue lysates were increased.We used adenovirus carrying CXCR4 gene to transfect MSCs in orderto increase engraftment number of MSCs at injured sites.Immunohistochemieal staining and flow cytometry analysisindicated that SDF-1/CXCR4 axis indeed improved numbers of exogenous MSCs transplanted in injured lung.However,engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis.We found that engraRment of MSCs almost differentiated into lung fibroblasts or myofibroblasts,rarely differentiated into lungepithelial cells.In the following research,we demonstrated that canonical Wnt/β-catenin signaling was activated in injured tissue and may be involved in regulating the differentiation of MSCs.In vitro study,we demonstrated that activation of the Wnt/β-catenin signaling could stimulate MSCs to express myofibroblasts markers,but this process was attenuated by Wnt antagonists DKK1.Our data demonstrated that SDF-1/CXCR4 axis is important in regulatingmigration of MSCs for lung repair or pulmonary fibrogenesis.Wnt signaling plays a key role in the regulation of MSCs differentiationand the pathogenesis of fibrotic diseases.We suggested that abnormal activated Wnt signalingwould play an important role in pulmonary fibrosis by indueingmyofibroblasts differentiation of MSCs.
lung injury mesenchymal stem cells (MSCs) pulmonary fibrosis SDF-1/CXCR4 Wnt/β-catenin signaling
Zhaorui Sun Shinan Nie
Jinling Hospital,Emergency Department,Nanjing University,School Medicine,Nanjing,210002,P.R.China;Mailing address:Emergency Department J,inling Hospital,School Medicine,Nanjing University,Zhongshan East Road 305,Nanjing,210002,P.R.China
国内会议
北京
英文
245-263
2013-04-12（万方平台首次上网日期，不代表论文的发表时间）