XB130 promotes bronchioalveolar stem cell and Club cell proliferation in airway epithelial repair and regeneration
| Autor: | Shaf Keshavjee, Hongmei Liu, Hae-Ra Cho, Ricardo Zamel, Hiroaki Toba, Yingchun Wang, Xiao-Hui Bai, Alonso Lira, Mingyao Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
small airway injury and repair
Fluorescent Antibody Technique Apoptosis Biology transgenic mice Real-Time Polymerase Chain Reaction bronchioalveolar duct junction Immunoenzyme Techniques Glycogen Synthase Kinase 3 Mice Phosphatidylinositol 3-Kinases Animals Regeneration RNA Messenger Protein kinase B Bronchioles PI3K/AKT/mTOR pathway Adaptor Proteins Signal Transducing Cell Proliferation Mice Knockout Wound Healing Glycogen Synthase Kinase 3 beta Cell growth Reverse Transcriptase Polymerase Chain Reaction Stem Cells Microfilament Proteins naphthalene Epithelial Cells Molecular biology Cell biology Mice Inbred C57BL Pulmonary Alveoli PI3K/Akt signaling Club cell Oncology Respiratory epithelium Female Stem cell Signal transduction Proto-Oncogene Proteins c-akt Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Proliferation of bronchioalveolar stem cells (BASCs) is essential for epithelial repair. XB130 is a novel adaptor protein involved in the regulation of epithelial cell survival, proliferation and migration through the PI3K/Akt pathway. To determine the role of XB130 in airway epithelial injury repair and regeneration, a naphthalene-induced airway epithelial injury model was used with XB130 knockout (KO) mice and their wild type (WT) littermates. In XB130 KO mice, at days 7 and 14, small airway epithelium repair was significantly delayed with fewer number of Club cells (previously called Clara cells). CCSP (Club cell secreted protein) mRNA expression was also significantly lower in KO mice at day 7. At day 5, there were significantly fewer proliferative epithelial cells in the KO group, and the number of BASCs significantly increased in WT mice but not in KO mice. At day 7, phosphorylation of Akt, GSK-3β, and the p85α subunit of PI3K was observed in airway epithelial cells in WT mice, but to a much lesser extent in KO mice. Microarray data also suggest that PI3K/Akt-related signals were regulated differently in KO and WT mice. An inhibitory mechanism for cell proliferation and cell cycle progression was suggested in KO mice. XB130 is involved in bronchioalveolar stem cell and Club cell proliferation, likely through the PI3K/Akt/GSK-3β pathway. |
| Databáze: | OpenAIRE |
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