Pleiotrophin Regulates Lung Epithelial Cell Proliferation and Differentiation during Fetal Lung Development via β-Catenin and Dlk1*
Autor: | Yujie Guo, Li Gao, Tingting Weng, Lin Liu, Deming Gou, Narendranath Reddy Chintagari, Kexiong Zhang, Manoj Bhaskaran, Jeyaparthasarathy Narayanaperumal |
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Jazyk: | angličtina |
Rok vydání: | 2009 |
Předmět: |
Cellular differentiation
Cell Notch signaling pathway Pleiotrophin Biochemistry Tissue Culture Techniques chemistry.chemical_compound Molecular Basis of Cell and Developmental Biology Fetus Pregnancy medicine Morphogenesis Animals RNA Small Interfering Promoter Regions Genetic Molecular Biology Lung Cells Cultured beta Catenin Cell Proliferation Midkine biology Cell growth Receptor-Like Protein Tyrosine Phosphatases Class 5 Membrane Proteins Tyrosine phosphorylation Cell Differentiation Epithelial Cells Cell Biology Cell biology Rats medicine.anatomical_structure chemistry biology.protein Cytokines Intercellular Signaling Peptides and Proteins Female Signal transduction Carrier Proteins TCF Transcription Factors Signal Transduction |
Popis: | The role of pleiotrophin in fetal lung development was investigated. We found that pleiotrophin and its receptor, protein-tyrosine phosphatase receptor beta/zeta, were highly expressed in mesenchymal and epithelial cells of the fetal lungs, respectively. Using isolated fetal alveolar epithelial type II cells, we demonstrated that pleiotrophin promoted fetal type II cell proliferation and arrested type II cell trans-differentiation into alveolar epithelial type I cells. Pleiotrophin also increased wound healing of injured type II cell monolayer. Knockdown of pleiotrophin influenced lung branching morphogenesis in a fetal lung organ culture model. Pleiotrophin increased the tyrosine phosphorylation of beta-catenin, promoted beta-catenin translocation into the nucleus, and activated T cell factor/lymphoid enhancer factor transcription factors. Dlk1, a membrane ligand that initiates the Notch signaling pathway, was identified as a downstream target of the pleiotrophin/beta-catenin pathway by endogenous dlk1 expression, promoter assay, and chromatin immunoprecipitation. These results provide evidence that pleiotrophin regulates fetal type II cell proliferation and differentiation via integration of multiple signaling pathways including pleiotrophin, beta-catenin, and Notch pathways. |
Databáze: | OpenAIRE |
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