| Objective:To investigate the effect and mechanism of Brahma-rela ted gene 1?Brg1?on the number and function of type 2 alveolar e-pith elial cells in C57BL/6 mice.Methods:6-8 weeks female C57BL/6 mice were used as wild type control group?WT?,and Brg1fl/fl group with Brg1 gene knockout in type II alveolar epithelial cells?n=8?.Immunohistochemistry and immunofluorescence was used to determine the number of Surfactantassocia-ted protein C?SFTPC?positive cells in the pulmonary alveoli.The percentage of Prosurfactant Protein C?pro SP-C?cells was analyzed by flow cytometry.Western blot was used to detected the expression levels of pro SP-C?SFTPC?Surfactantassociated protein A?SFTPA?and Surfact-antassociated protein D?SFTPD?in lung tissue of each group.The expression levels of CyclinD1 and the key proteins EGFR,p-EGFR,PI3K,p-PI3K,AKT,p-AKT,NF-?B p65 in the proliferation-related signal transduction pathway were detected by Western blot.Results:Anti-SFTPC immunohistochemistry and immunofluores-ce nce showed that the number of SFTPC positive cells in Brg1fl/fl mice w as significantly higher than that in WT mice?P<0.05?.The flow cyto-m etry showed that the percentage of pro SP-C positive cells significantly increased in the Brg1fl/fl group?p<0.05?.AECIIs secreting functional prot eins pro SP-C,SFTPC,SFTPA and SFTPD were significantly increased in Brg1fl/fl mice?P<0.05?;Knockout of Brg1 promoted the expression of NF-?B p65 and CyclinD1?p<0.05?.The ratios of p-EGFR/EGFR?p-PI3K/PI3K and p-AKT/AKT in Brg1fl/fl mice were significantly increa sed?p<0.05?.Conclusion:Specific knockout of Brg1 in type?alveolar epithelial cells of C57BL/6 mice could increase the number and function of AECIIs.The possible mechanism was that knocking out Brg1 promoted the activation of EGFR/PI3K/AKT/NF-?B signaling pathway,and increasing the expression of the protein CyclinD1,which lead to an increasing in the number and secreted protein of AECIIs in mice. |
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