title: XB130 promotes bronchioalveolar stem cell and Club cell proliferation in airway epithelial repair and regeneration.
abstract: 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.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Toba
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Zamel
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada.
authors.forename: Hae-Ra
authors.initials: HR
authors.lastname: Cho
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada.
authors.forename: Alonso
authors.initials: A
authors.lastname: Lira
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada.|Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.|Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada.|Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.|Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D055745:Bronchioles / Q000166:cytology* / Q000502:physiology; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014945:Wound Healing
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008840:Microfilament Proteins; D012333:RNA, Messenger; C000603973:XB130 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: PI3K/Akt signaling; bronchioalveolar duct junction; naphthalene; small airway injury and repair; transgenic mice