title: [Dynamic changes of adenomatous polyposis coli protein and glycogen synthase kinase 3beta in the repair of the injured airway epithelial cells in smoking mice].
abstract: To investigate the roles of adenomatous polyposis coli (APC) protein and glycogen synthase kinase 3beta (GSK3beta) of smoking murine model in the repair of the injured airway epithelial cells (AECs) in different stages, 30 male Kun-Ming mice were randomly divided into two groups, the control group and the smoking group. There were 24 mice in smoking group, and 6 animals were separately killed at the end of the 1st, 4th, 8th and 12th week after smoking. Then the following tests were undertaken: (1) HE staining of lung section to observe the morphological changes of the bronchi in the smoking mice. (2) Immunohistochemical staining of APC protein and GSK3beta in the AECs. (3) Western blot was used to detect the levels of APC protein, GSK3beta and phosphorated GSK3beta (p-GSK3beta) in pulmonary tissue. (4) Observing the localizations of APC protein and GSK3beta in the AECs by immunofluorescence technique. The results showed: (1) AECs showed changes of predominant injury (1-, 4-week), repair (8-week) and reinjury (12-week) along with smoking time prolonged. The experimental results indicated that the model of smoking mice was duplicated successfully. (2) Immunohistochemical results showed that the expression of APC protein in the AECs increased after 1-week smoking (0.458 +/- 0.062 vs 0.399 +/- 0.060, P< 0.05 vs control), but was significantly decreased at the end of the 4th week (0.339+/- 0.056, P<0.01 vs control) and increased at the end of the 8th and 12th week (0.387 +/- 0.041, 0.378 +/- 0.037, P<0.05 vs 4-week). The expression of GSK3beta in the AECs of smoking mice obviously decreased (P<0.01 or P<0.05 vs control). (3) Western blot showed that the expressions of APC protein and GSK3beta in lung tissue were consistent with the results of immunohistochemistry; and the levels of p-GSK3beta in all smoking models were higher than that in control. (4) The results of immunofluorescence showed that APC protein was localized mainly near the regions of epithelial cell membrane at the end of the 1st and 8th week after smoking, which were dissimilar with the localization in control, and this change was not seen in the location of GSK3beta. Taken together, these results demonstrate that the expressions and localizations of APC protein, GSK3beta and the activity of GSK3beta are dynamically changed in the AECs with experimental smoking injury at different phases, suggesting that APC protein and GSK3beta may be involved in the regulation of migration and proliferation of AECs, and play an important role in the process of repair of airway epithelium injury.
authors.affiliation: Department of Pathology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ming-Ge
authors.initials: MG
authors.lastname: Liu
authors.forename: Na-Ping
authors.initials: NP
authors.lastname: Li
authors.forename: Ren-Liang
authors.initials: RL
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Yuan-Zhi
authors.initials: YZ
authors.lastname: Hong
authors.forename: Dan
authors.initials: D
authors.lastname: Tian
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D001980:Bronchi / Q000473:pathology / Q000502:physiology*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008168:Lung / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D012038:Regeneration; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D012906:Smoke; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3