Repair of naphthalene-induced acute tracheal injury by basal cells depends on ß-catenin.
J Thorac Cardiovasc Surg
; 148(1): 322-32, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24280717
ABSTRACT
OBJECTIVES:
Little is known about the role of Wnt/ß-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 ß-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 ß-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 ß-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. ß-Catenin is required for proliferation and self-renewal of tracheal epithelial cells.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Células-Tronco
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Traqueia
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Mucosa Respiratória
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Proliferação de Células
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Células Epiteliais
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Beta Catenina
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Naftalenos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article