局部雌激素作用下大鼠阴道萎缩的蛋白质组学及生物信息学分析OA

Objective To investigate the differentially expressed proteins(DEPs)in rats with vaginal atrophy before and after the local estrogen treatment using proteomics combined with bioinformatics,and speculate the possible functional mechanism.Methods Thirty-six healthy 6-8-week-old female reproductive age non-pregnant SD rats were divided into three groups:ovariectomized(OVX)group,ovariectomized+local estrogen treatment group(OVX+E2),and sham group.Vaginal specimens from the three groups were collected to screen DEPs by non-labeled quantitative proteomics analysis.The significant DEPs related to estrogen metabolism after local estrogen treatment were further screened.GO and KEGG analyses of these proteins were performed to speculate on the possible mechanism.Results A total of 102 DEPs were screened between OVX+E2 group and OVX group,among which 74 were up-regulated and 28 were down-regulated.A total of 655 DEPs were screened between sham group and OVX group,among which 494 were up-regulated and 161 were down-regulated.Of DEPs between OVX+E2 group and OVX group,Shc-transforming protein 1,a differential protein associated with the estrogen metabolism pathway,was up-regulated.Of DEPs between sham group and OVX group,all identified differential proteins related to estrogen metabolism were up-regulated,including matrix metalloproteinase-9(MMP-9),shc-transforming protein 1,and multiple keratins(KRT14,KRT42,KRT35,KRT33B,KRT23,and KRT17).Of the DEPs between OVX+E2 group and OVX group,the significantly different pathway involved in Shc-transforming protein 1 was the Shc-EGFR complex by GO analysis,and the phosphotyrosine residue binding by molecular function analysis.KEGG pathway analysis indicated the significantly up-regu-lated pathway involved in Shc-transforming protein 1 was the bacterial invasion pathway of epithelial cells.Furthermore,the protein correlation analysis of DEPs showed that Shc-transforming protein 1 was significantly correlated with pseudopodium-enriched atypical kinase 1,paxillin,and MHC class Ⅱ antigen.Conclusion Local estrogen treatment may improve the vaginal atrophy in castrated rats by up-regulating Shc-transforming protein 1.The Shc-transforming protein 1 may exert its function by forming the shc-EGFR complex to affect the binding of phosphotyrosine residues,participate in the bacterial invasion pathway of epithelial cells,and form an interaction network with atypical kinase 1,spike protein,and MHC class Ⅱ antigens.