2026年 03期

摘要(Abstract)：

为了探究新型冠状病毒刺突蛋白S1调控气道黏蛋白基因表达的潜在机制，采用一定含量的刺突蛋白S1刺激人肺上皮细胞BEAS-2B,检测其对主要黏蛋白表达的影响；通过生物信息学预测与黏蛋白启动子区域结合的转录因子，并选择重叠的转录因子进行后续研究；采用基因干扰、染色质免疫共沉淀和双荧光素酶报告基因实验验证上述转录因子与黏蛋白启动子区域的结合，通过基因干扰和蛋白质免疫印迹法探究刺突蛋白S1调控黏蛋白表达的信号通路。结果表明：刺突蛋白S1刺激气道上皮细胞后，能导致黏蛋白表达增加，转录因子c-Myc可与黏蛋白的启动子区域直接结合；干扰刺突蛋白S1受体ACE2基因后，磷酸化蛋白激酶B(AKT)、 c-Myc和黏蛋白(MUC)的表达量均减小，表明刺突蛋白S1通过ACE2/AKT/c-Myc/MUC信号通路调控黏蛋白的表达。

关键词(KeyWords)：生物信息学;刺突蛋白;气道黏蛋白;转录调控;转录因子

基金项目(Foundation):国家自然科学基金项目(12272063)

作者(Author):张雪茹,郭佳,罗明志,张赛帅,邓林红

DOI:10.13349/j.cnki.jdxbn.20260310.001

参考文献(References)：

[1] LU W J,LIU X Q,WANG T,et al.Elevated MUC1 and MUC5AC mucin protein levels in airway mucus of critical ill COVID-19 patients[J].Journal of Medical Virology,2021,93(2):582.

[2] HE J P,CAI S J,FENG H J,et al.Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients[J].Protein & Cell,2020,11(9):680.

[3] ABRAMI M,BIASIN A,TESCIONE F,et al.Mucus structure,viscoelastic properties,and composition in chronic respiratory diseases[J].International Journal of Molecular Sciences,2024,25(3):1933.

[4] CHATTERJEE M,VAN PUTTEN J P M,STRIJBIS K.Defensive properties of mucin glycoproteins during respiratory infections-relevance for SARS-CoV-2[J].mBio,2020,11(6):e02374-20.

[5] KATO T,ASAKURA T,EDWARDS C E,et al.Prevalence and mechanisms of mucus accumulation in COVID-19 lung disease[J].American Journal of Respiratory and Critical Care Medicine,2022,206(11):1336.

[6] FAHY J V,DICKEY B F.Airway mucus function and dysfunction[J].New England Journal of Medicine,2010,363(23):2233.

[7] BAUTISTA M V,CHEN Y,IVANOVA V S,et al.IL-8 regulates mucin gene expression at the posttranscriptional level in lung epithelial cells[J].Journal of Immunology,2009,183(3):2159.

[8] BASBAUM C,LEMJABBAR H,LONGPHRE M,et al.Control of mucin transcription by diverse injury-induced signaling pathways[J].American Journal of Respiratory and Critical Care Medicine,1999,160(5 Pt 2):S44.

[9] LI Y,TANG X X.Abnormal airway mucus secretion induced by virus infection[J].Frontiers in Immunology,2021,12:701443.

[10] 杨海龙，刘允，杨斌.新冠病毒刺突蛋白及其受体的结构与相互作用[J].大学化学，2020,35(12):2.

[11] LI F.Structure,function,and evolution of coronavirus spike proteins[J].Annual Review of Virology,2016,3(1):237.

[12] LI F,LI W H,FARZAN M,et al.Structure of SARS coronavirus spike receptor-binding domain complexed with receptor[J].Science,2005,309(5742):1864.

[13] BASILE M S,CAVALLI E,MCCUBREY J,et al.The PI3K/AKT/mTOR pathway:a potential pharmacological target in COVID-19[J].Drug Discovery Today,2022,27(3):848.

[14] KIM S Y,JIN W,SOOD A,et al.Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions[J].Antiviral Research,2020,181:104873.

[15] CHENG J,YANG H,CHEN F,et al.The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/AKT signaling[J].Translational Neuroscience,2024,15(1):20220334.

[16] 唐欣，万南生，杨夏，等.慢性气道黏液高分泌与慢性阻塞性肺疾病的研究进展[J].中华结核和呼吸杂志，2021,44(6):574.

[17] 邢越，王健，陈豫钦.新型冠状病毒对肺气血屏障结构和功能的影响及机制研究进展[J] .国际呼吸杂志，2021,41(8):572-576.

[18] MEYERHOLZ D K,REZNIKOV L R.Influence of SARS-CoV-2 on airway mucus production:a review and proposed model[J].Veterinary Pathology,2022,59(4):578.

[19] ZHAO X P,YANG L P.Pharmacological targets and validation of remdesivir for the treatment of COVID-19-associated pulmonary fibrosis:a network-based pharmacology and bioinformatics study[J].Medicine,2024,103(39):e39062.

[20] AL-MAGHREBI M,RENNO W M.The tACE/Angiotensin (1-7)/Mas axis protects against testicular ischemia reperfusion injury[J].Urology,2016,94:312.e1.

[21] PATEL Y,THAPA P,PRAJAPATI A.New insights into pro-state cancer from the renin-angiotensin-aldosterone system[J].Cellular Signalling,2024,124:111442.

[22] CAO X,YANG F Y,SHI T T,et al.Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis activates AKT signaling to ameliorate hepatic steatosis[J].Scientific Reports,2016,6:21592.

[23] ZHANG A J,AI L M.Xanthine negatively regulates c-MYC through the PI3K/AKT signaling pathway and inhibits the proliferation,invasion,and migration of breast cancer cells[J].Asia-Pacific Journal of Clinical Oncology,2025,21(1):3.

[24] GUO C H,ZHANG Y Y,LIU L,WAN Y F.AKT modulates PTEN expression in hepatocarcinoma HepG2 cells via c-MYC pathway[J].Tumor,2020,40(2):102.