解放军医学杂志2026,Vol.51Issue(3):427-434,8.DOI:10.11855/j.issn.0577-7402.1846.2025.1218
miR-22-3p调控TXNIP对肺炎链球菌诱导的肺泡上皮细胞增殖及凋亡的影响
Effects of miR-22-3p on Streptococcus pneumoniae-induced proliferation and apoptosis of alveolar epithelial cells by regulating TXNIP
摘要
Abstract
Objective To investigate the effects of microRNA-22-3p(miR-22-3p)on the proliferation and apoptosis of alveolar epithelial cells induced by Streptococcus pneumoniae(S.pneumoniae),as well as the targeting relationship between miR-22-3p and thioredoxin-interacting protein(TXNIP).Methods Alveolar type Ⅱ epithelial cells(AEC Ⅱ)were randomly divided into 8 groups:control group,model group,miR-NC group,miR-22-3p mimics group,si-NC group,si-TXNIP group,miR-22-3p mimics+pcDNA3.1 group,and miR-22-3p mimics+pcDNA3.1-TXNIP group.Cells in control group received no treatment,while those in model group were infected with S.pneumoniae.Cells in other groups were transfected with miRNA or DNA prior to S.pneumoniae infection.The expression levels of miR-22-3p and TXNIP mRNA were detected by quantitative real-time polymerase chain reaction(q RT-PCR).Cell proliferation ability was assessed using the cell counting Kit-8(CCK-8)assay.Cell apoptosis was detected by Annexin V staining.The levels of interleukin(IL)-6 and IL-10 were measured by enzyme-linked immunosorbent assay(ELISA).The protein expression levels of B-cell lymphoma-2(Bcl-2)-associated X protein(Bax),Bcl-2,Cleaved caspase-3,and TXNIP were determined by Western blotting.A dual-luciferase reporter assay was performed to verify the targeted regulatory relationship between miR-22-3p and TXNIP.Results Compared with control group,model group showed decreased cell proliferation ability,as well as reduced expression levels of miR-22-3p,IL-10,and Bcl-2 protein(P<0.05),while exhibiting increased cell apoptosis rate,along with elevated expression levels of TXNIP mRNA,IL-6,Bax,Cleaved caspase-3,and TXNIP protein(P<0.05).Compared with model group and miR-NC group,miR-22-3p mimics group exhibited enhanced cell proliferation ability,and increased expression levels of miR-22-3p,IL-10,and Bcl-2 protein(P<0.05),while the cell apoptosis rate and expression levels of TXNIP mRNA,IL-6,Bax,Cleaved caspase-3,and TXNIP protein were significantly reduced(P<0.05).For si-TXNIP group,there was no significant difference in the expression levels of miR-22-3p compared with model group and miR-NC group(P>0.05),but cell proliferation ability and the expression levels of IL-10 and Bcl-2 protein were increased(P<0.05),and the cell apoptosis rate and expression levels of TXNIP mRNA,IL-6,Bax,Cleaved caspase-3,and TXNIP protein were decreased(P<0.05).Compared with miR-22-3p mimics group and miR-22-3p mimics+pcDNA3.1 group,miR-22-3p mimics+pcDNA3.1-TXNIP group showed no significant change in the expression levels of miR-22-3p expression(P>0.05),but decreased cell proliferation ability and reduced expression levels of IL-10 and Bcl-2 protein(P<0.05),along with increased cell apoptosis rate and elevated expression levels of TXNIP mRNA,IL-6,Bax,Cleaved caspase-3,and TXNIP protein(P<0.05).Dual-luciferase reporter assay confirmed that miR-22-3p could directly bind to TXNIP.Conclusions Overexpression of miR-22-3p can downregulate the expression of TXNIP,thereby inhibiting the apoptosis and promoting the proliferation of alveolar epithelial cells infected with S.pneumoniae.关键词
微小RNA-22-3p/硫氧还蛋白互作蛋白/肺炎链球菌/肺泡上皮细胞/增殖/凋亡Key words
microRNA-22-3p/thioredoxin-interacting protein/Streptococcus pneumoniae/alveolar epithelial cells/proliferation/apoptosis分类
医药卫生引用本文复制引用
朱慧敏,王军,张婵,孔维康..miR-22-3p调控TXNIP对肺炎链球菌诱导的肺泡上皮细胞增殖及凋亡的影响[J].解放军医学杂志,2026,51(3):427-434,8.基金项目
This work was supported by the Shandong Provincial Medical and Health Science and Technology Development Plan(202006011247) 山东省医药卫生科技发展计划(202006011247) (202006011247)