lncRNA MALAT1对哮喘小鼠Th17/Treg细胞平衡的影响

摘要
图/表
参考文献(0)
相关文章 (15)

全文: PDF (1350 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要 目的： 检测长链非编码RNA（lncRNA）肺腺癌转移相关转录本1（metastasis associated in lung denocarcinoma transcript 1，MALAT1）对哮喘小鼠Th17/Treg细胞平衡的影响。方法: 将6~8周龄雄性BALB/c小鼠随机分成对照组和哮喘组，每组10只。用卵清蛋白诱导小鼠支气管哮喘模型，HE染色和PAS染色观察小鼠肺组织病理改变，流式细胞术检测小鼠脾细胞中的Th17细胞和Treg细胞，qRT-PCR检测脾组织中lncRNA MALAT1及Rorc/Foxp3的表达水平。结果: 与对照组相比，哮喘组小鼠气道炎症变化明显，支气管周围存在明显的炎性细胞浸润，管壁增厚，气道上皮细胞破坏或不规则。哮喘组小鼠脾组织中Th17细胞比例显著升高（P<0.01），Th17细胞的关键转录因子维甲酸相关孤儿核受体C（retinoic acid receptor related orphan C，Rorc）表达上调（P<0.05），而Treg细胞比例显著下降（P<0.01），其关键转录因子叉状头/翼状螺旋转录因子P3（forkhead/winged helix transcriptional factor P3，Foxp3）表达下调（P<0.05）；脾组织lncRNA MALAT1相对表达量显著上升（P<0.01），与Th17细胞比例呈正相关（r=0.64，P<0.05），与Treg细胞呈负相关（r=-0.73，P<0.05）；而且MALAT1的表达与Rorc表达呈正相关（r=0.65，P<0.05），与Foxp3表达呈负相关（r=-0.60，P<0.05）。结论: MALAT1与哮喘小鼠Th17/Treg细胞的失衡密切相关，靶向于MALAT1可能有助于改善哮喘小鼠Th17/Treg平衡。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	朱海金1
	王诏玉1
	单文琪1
	王影1
	常明1
	汪雪峰2

关键词 ：哮喘, 肺腺癌转移相关转录本1(MALAT1), Th17细胞, Treg细胞

Abstract：Objective： To detect the relationship between the long-chain non coding RNA （lncRNA） metastasis associated in lung denocarcinoma transcript 1 (MALAT1) and the balance of Th17/Treg in asthmatic mice. Methods： BALB/c male mice at age of 6-8 weeks were randomly divided into control group and asthma group, with 10 mice in each group. The group of asthmatic mice was established by ovalbumin. HE staining and PAS staining were used to observe the pathological changes of lung tissue. Flow cytometry was used to detect Th17/Treg in spleen cells, and realtime fluorescence quantitative PCR was used to detect the expression level of lncRNA MALAT1 and Rorc/Foxp3 in spleen tissue. Results： Compared with the control group, the airway inflammation of asthmatic mice was significantly changed, with obvious infiltration of inflammatory cells around the bronchus, thickening of the wall, and destruction or irregularity of airway epithelial cells. The proportion of Th17 in the spleen tissue was significantly increased (P<0.01), and the expression of retinoic acid receptor related orphan C (Rorc) was also up-regulated (P<0.05), while the proportion of Treg was significantly decreased (P<0.01), the expression of forkhead/winged helix transcriptional factor P3 (Foxp3) was down-regulated (P<0.05). The relative expression of lncRNA MALAT1 in spleen tissue was significantly increased (P<0.01), positively correlated with the proportion of Th17 cells (r=0.64, P<0.05), and negatively correlated with Treg cells (r=-0.73, P<0.05). Moreover, MALAT1 expression was positively correlated with Rorc expression (r=0.65, P<0.05), and negatively correlated with Foxp3 expression (r=-0.60, P<0.05). Conclusion： MALAT1 is involved in regulating the balance of Th17/Treg in asthmatic mice, which may help to develop therapeutic methods to improve asthma inflammation.

收稿日期: 2022-11-08

基金资助:国家自然科学基金资助项目（81871243）；江苏省社会发展项目（BE2017697）；江苏省妇幼健康科研项目（F202067）；镇江市中医妇科疾病临床研究中心开放性课题（SS202204-KFB02）

通讯作者: 常明（通讯作者），主任医师，硕士生导师，E-mail：changming8@163.com；汪雪峰（通讯作者），研究员，博士生导师，E-mail： xuefengwang@ujs.edu.cn

作者简介: 朱海金（1996—），男，硕士研究生

引用本文:

朱海金1，王诏玉1，单文琪1，王影1，常明1，汪雪峰2. lncRNA MALAT1对哮喘小鼠Th17/Treg细胞平衡的影响[J]. 江苏大学学报:医学版, 2023, 33(05): 420-425. ZHU Haijin1, WANG Zhaoyu1, SHAN Wenqi1, WANG Ying1, CHANG Ming1, WANG Xuefeng2. Effect of lncRNA MALAT1 on Th17/Treg cell balance in asthmatic mice#br#. Journal of Jiangsu University(Medicine Edition), 2023, 33(05): 420-425.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2023/V33/I05/420

［1］Mims JW. Asthma: definitions and pathophysiology［J］. Int Forum Allergy Rhinol, 2015, 5 Suppl 1: S2-S6.
［2］MenziesGow A, Ying S, Sabroe I, et al. Eotaxin (CCL11) and eotaxin2 (CCL24) induce recruitment of eosinophils, basophils, neutrophils, and macrophages as well as features of early and latephase allergic reactions following cutaneous injection in human atopic and nonatopic volunteers［J］. J Immunol, 2002, 169 (5): 2712-2718.
［3］Shrestha Palikhe N, Wu Y, Konrad E, et al. Th2 cell markers in peripheral blood increase during an acute asthma exacerbation［J］. Allergy, 2021, 76: 281-290.
［4］Newcomb DC, Peebles RS Jr. Th17mediated inflammation in asthma［J］. Curr Opin Immunol, 2013, 25: 755-60.
［5］Lee GR. The Balance of Th17 versus Treg cells in autoimmunity［J］. Int J Mol Sci, 2018, 19(3): 730.
［6］Xing C, Sun SG, Yue ZQ, et al. Role of lncRNA LUCAT1 in cancer［J］. Biomed Pharmacother, 2021, 134: 111158.
［7］Li L, Li QH, Hao WM, et al. Upregulation of lncRNA MALAT1 induced proliferation and migration of airway smooth muscle cells via miR150eIF4E/Akt signaling［J］. Front Physiol, 2019, 10: 1337.
［8］Zhang X, Hamblin MH, Yin KJ. The long noncoding RNA MALAT1: Its physiological and pathophysiological functions［J］. RNA Biol, 2017, 14: 1705-1714.
［9］Feng H, Xiong X, Chen Z, et al. MALAT1 induces food allergy by promoting release of IL6 from dendritic cells and suppressing the immunomodulatory function of Tregs［J］. J Asthma Allergy, 2022, 15: 529-544.
［10］王婷, 单文琪, 薛菲, 等. 日本血吸虫多肽SJMHE1通过抑制哮喘小鼠肺组织中Th2细胞和ILC2反应减轻小鼠气道炎症［J］. 细胞与分子免疫学杂志, 2021, 37(12): 1106-1110.
［11］Monticelli LA, Osborne LC, Noti M, et al. IL33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulinEGFR interactions［J］. Proc Natl Acad Sci U S A, 2015, 112: 10762-10767.
［12］Gans MD, Gavrilova T. Understanding the immunology of asthma: Pathophysiology, biomarkers, and treatments for asthma endotypes［J］. Paediatr Respir Rev, 2020, 36: 118-127.
［13］Hammad H, Lambrecht BN. The basic immunology of asthma［J］. Cell, 2021, 184(9): 2521-2522.
［14］Boonpiyathad T, Szener ZC, Satitsuksanoa P, et al. Immunologic mechanisms in asthma［J］. Semin Immunol, 2019, 46: 101333.
［15］Maggi L, Mazzoni A, Capone M, et al. The dual function of ILC2: From host protection to pathogenic players in type 2 asthma［J］. Mol Aspects Med, 2021, 80: 100981.
［16］Wallrapp A, Riesenfeld SJ, Burkett PR, et al. The neuropeptide NMU amplifies ILC2driven allergic lung inflammation［J］. Nature, 2017, 549(7672): 351-356.
［17］Zou XL, Chen ZG, Zhang TT, et al. Th17/Treg homeostasis, but not Th1/Th2 homeostasis, is implicated in exacerbation of human bronchial asthma［J］. Ther Clin Risk Manag, 2018, 14: 1627-1636.
［18］薛菲, 余孟珠, 单文琪, 等. 哮喘小鼠脾细胞中粒细胞型髓源性抑制细胞和Th17细胞水平的变化［J］. 江苏大学学报(医学版), 2020, 30(5): 414-417, 422.
［19］Bocchetti M, Scrima M, Melisi F, et al. LncRNAs and immunity: coding the immune system with noncoding oligonucleotides［J］. Int J Mol Sci, 2021, 22(4): 1741.
［20］Gutschner T, Hmmerle M, Eissmann M, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells［J］. Cancer Res, 2013, 73: 1180-1189.
［21］Guo F, Yuan Y, Chen Z, et al. Downregulation of the long noncoding RNA MALAT1 in tenofovirtreated pregnant women with hepatitis B virus infection promotes immune recovery of natural killer cells via the hasmiR1555p/HIF1α axis［J］. Int Immunopharmacol, 2022, 107: 108701.
［22］袁星星, 王雪慧, 王瑶, 等. 平喘颗粒通过lncRNA MALAT1/miR1405p/VEGFA抑制哮喘气道血管新生的作用机制［J］. 中华中医药杂志, 2021, 36(4): 2006-2012.
［23］Huang J, Wang FH, Wang L, et al. LncRNA MALAT1 promotes proliferation and migration of airway smooth muscle cells in asthma by downregulating microRNA216a［J］. Saudi J Biol Sci, 2021, 28(8): 4124- 4131.
［24］Liang Z, Tang F. The potency of lncRNA MALAT1/miR155/CTLA4 axis in altering Th1/Th2 balance of asthma［J］. Biosci Rep, 2020, 40(2): BSR20190397.
［25］Li Z, Zhang Q, Wu Y, et al. lncRNA MALAT1 modulates the maturation process, cytokine secretion and apoptosis in airway epithelial cellconditioned dendritic cells［J］. Exp Ther Med, 2018, 16(5): 3951-3958.