XB130 promotes bronchioalveolar stem cell and Club cell proliferation in airway epithelial repair and regeneration
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Hiroaki Toba1, Yingchun Wang1, Xiaohui Bai1, Ricardo Zamel1, Hae-Ra Cho1, Hongmei Liu1, Alonso Lira1, Shaf Keshavjee1,2,3, Mingyao Liu1,2,3
1Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, Universal Health Network, Toronto, ON, Canada
2Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
3Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
Mingyao Liu, e-mail: firstname.lastname@example.org
Keywords: naphthalene, small airway injury and repair, bronchioalveolar duct junction, PI3K/Akt signaling, transgenic mice
Received: July 09, 2015 Accepted: August 21, 2015 Published: September 03, 2015
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.
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