Objectives Little is known about the role of Wnt/β-catenin in postnatal airway homeostasis and basal cell function. This study aimed to investigate the role of Wnt signaling in the self-renewal of basal cells and the involvement of β-catenin in tracheal repair after naphthalene-induced injury. Methods Mice were treated with naphthalene and injected with 4-hydroxytamoxifen. Injury and repair of the tracheal epithelium after naphthalene-mediated secretory cell depletion was assessed by a immunohistochemical study. The involvement of Wnt and β-catenin signaling in basal cell proliferation was investigated during in vitro expansion. Results Immunohistochemical analysis of tracheal epithelium in wild-type mice showed a reduction in the number of Clara cell secretory protein (CCSP+) and forkhead box transcription factor (Fox-J1+) cells on days 2 to 5 after naphthalene-induced injury; this cell population was regenerated by day 10. After flush labeling, bromodeoxyuridine-positive (BrdU+) cells and Ki67+ cells were observed in tracheal epithelium on days 2 to 5 but not on days 10 and 21. Confocal microscopy visualizing K5+ and BrdU+ cells showed that Wnt3a promotes proliferation of K5+ cells. Immunohistochemical analysis of K5+ and CCSP+ in tracheal epithelial cells from wild-type littermate and K5-Cre-mediated β-catenin knock-out mice showed that on day 3, the number of CCSP+ cells was decreased in all mice. On day 10, CCSP+ cells were present in wild-type littermate mice but absent in conditional knock-out mice. Conclusions Basal cells serve as stem cells in the tracheal epithelium, regenerating and maintaining tracheal epithelial cells in a mouse model of tracheal injury. β-Catenin is required for proliferation and self-renewal of tracheal epithelial cells. © 2014 by The American Association for Thoracic Surgery.
Hsu, H. S., Liu, C. C., Lin, J. H., Hsu, T. W., Su, K., & Hung, S. C. (2014). Repair of naphthalene-induced acute tracheal injury by basal cells depends on β-catenin. Journal of Thoracic and Cardiovascular Surgery, 148(1), 322–332. https://doi.org/10.1016/j.jtcvs.2013.10.039