微小RNA调控系统性硬皮病纤维化相关信号通路的研究进展

doi:10.35541/cjd.20230730

中华皮肤科杂志 ›› 2024, e20230730.doi: 10.35541/cjd.20230730

微小RNA调控系统性硬皮病纤维化相关信号通路的研究进展

徐经纬1 陈爽1 郭克磊2 韩立2 卞华1，2

¹河南中医药大学骨伤学院，郑州 450000；²南阳理工学院河南省张仲景方药与免疫调节重点实验室，南阳 473004

收稿日期:2023-12-12 修回日期:2024-04-28 发布日期:2024-05-24
通讯作者: 卞华 E-mail:biancrown@163.com
基金资助:
国家自然科学基金（82074415）；“中原英才计划（育才系列）”中原科技创新领军人才项目（234200510006）；河南省科技发展计划项目（232102311201）

MicroRNAs regulating signaling pathways related to systemic scleroderma fibrosis

Xu Jingwei¹, Chen Shuang¹, Guo Kelei², Han Li², Bian Hua^1,2

¹College of Bone Injury, Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China; ²Nanyang Institute of Technology, Zhang Zhongjing Key Laboratory of Prescriptions and Immune Regulation in Henan Province, Nanyang 473004, Henan, China

Received:2023-12-12 Revised:2024-04-28 Published:2024-05-24
Contact: Bian Hua E-mail:biancrown@163.com
Supported by:
National Natural Science Foundation of China （82074415）; Program for Leading Talents of Science and Technology Innovation in the Central Plain of China （234200510006）; Project for Science and Technology Development of Henan Province （232102311201）

摘要/Abstract

摘要： 【摘要】系统性硬皮病是一种累及皮肤和多个内脏的纤维化疾病，目前认为其主要由成纤维细胞异常活化、分泌过多的细胞外基质所致。越来越多的证据显示，与系统性硬皮病纤维化相关的信号级联包括转化生长因子β/Smads、Notch、Wnt/β连环素、大鼠肉瘤/细胞外调节蛋白激酶等。微小RNA参与不同靶基因的转录后调节并控制细胞状态，决定了由各种细胞信号级联反应引起的转录组和蛋白质组的变化。本文综述近年来微小RNA在系统性硬皮病纤维化相关信号通路中的调控作用以及可能的治疗靶点研究进展。

关键词: 硬皮病, 系统性, 微RNAs, 信号传导, 成纤维细胞

Abstract: 【Abstract】 Systemic scleroderma （SSc） is a fibrotic disease involving the skin and a variety of internal organs, which is currently thought to be mainly caused by abnormal activation of fibroblasts and excessive secretion of extracellular matrix. Growing evidence has shown signaling cascades associated with SSc fibrosis, including transforming growth factor-β/Smads, Notch, Wnt/β-catenin, rat sarcoma/extracellular regulated protein kinases, etc. MicroRNAs participate in the post-transcriptional regulation of different target genes and control the cell state, determining the changes in transcriptome and proteome caused by various cellular signaling cascades. This review summarizes recent research progress in the regulatory role of microRNAs in SSc fibrosis-related signaling pathways and potential therapeutic targets.

Key words: Scleroderma, systemic, MicroRNAs, Signal transduction, Fibroblasts

徐经纬陈爽郭克磊韩立卞华. 微小RNA调控系统性硬皮病纤维化相关信号通路的研究进展[J]. 中华皮肤科杂志, 2024,e20230730. doi:10.35541/cjd.20230730

Xu Jingwei, Chen Shuang, Guo Kelei, Han Li, Bian Hua, . MicroRNAs regulating signaling pathways related to systemic scleroderma fibrosis[J]. Chinese Journal of Dermatology,2024,e20230730. doi:10.35541/cjd.20230730

参考文献 34

［1］	Juhl P, Bondesen S, Hawkins CL, et al. Dermal fibroblasts have different extracellular matrix profiles induced by TGF⁃β, PDGF and IL⁃6 in a model for skin fibrosis［J］. Sci Rep, 2020,10（1）:17300. doi: 10.1038/s41598⁃020⁃74179⁃6.
［2］	Korman B. Evolving insights into the cellular and molecular pathogenesis of fibrosis in systemic sclerosis［J］. Transl Res, 2019,209:77⁃89. doi: 10.1016/j.trsl.2019.02.010.
［3］	Liu J, Yang T, Huang Z, et al. Transcriptional regulation of nuclear miRNAs in tumorigenesis （review）［J］. Int J Mol Med, 2022,50（1）:92 ［pii］. doi: 10.3892/ijmm.2022.5148.
［4］	Zhou B, Zuo XX, Li YS, et al. Integration of microRNA and mRNA expression profiles in the skin of systemic sclerosis patients［J］. Sci Rep, 2017,7:42899. doi: 10.1038/srep42899.
［5］	Suzuki HI. MicroRNA control of TGF⁃β signaling［J］. Int J Mol Sci, 2018,19（7）:1901. doi: 10.3390/ijms19071901.
［6］	Wang L, Li T, Ma X, et al. Exosomes from human adipose⁃derived mesenchymal stem cells attenuate localized scleroderma fibrosis by the let⁃7a⁃5p/TGF⁃βR1/Smad axis［J］. J Dermatol Sci, 2023,112（1）:31⁃38. doi: 10.1016/j.jdermsci.2023.09.001.
［7］	Shi X, Liu Q, Li N, et al. MiR⁃3606⁃3p inhibits systemic sclerosis through targeting TGF⁃β type Ⅱ receptor［J］. Cell Cycle, 2018,17（16）:1967⁃1978. doi: 10.1080/15384101.2018. 1509621.
［8］	Li Y, Huang J, Hu C, et al. MicroRNA⁃320a: an important regulator in the fibrotic process in interstitial lung disease of systemic sclerosis［J］. Arthritis Res Ther, 2021,23（1）:21. doi: 10.1186/s13075⁃020⁃02411⁃9.
［9］	Baral H, Uchiyama A, Yokoyama Y, et al. Antifibrotic effects and mechanisms of mesenchymal stem cell⁃derived exosomes in a systemic sclerosis mouse model: possible contribution of miR⁃196b⁃5p［J］. J Dermatol Sci, 2021,104（1）:39⁃47. doi: 10.1016/j.jdermsci.2021.08.006.
［10］	Chouri E, Servaas NH, Bekker C, et al. Serum microRNA screening and functional studies reveal miR⁃483⁃5p as a potential driver of fibrosis in systemic sclerosis［J］. J Autoimmun, 2018,89:162⁃170. doi: 10.1016/j.jaut.2017.12.015.
［11］	Cheng Z, Zhang J, Deng W, et al. Bushen Yijing Decoction （BSYJ） exerts an anti⁃systemic sclerosis effect via regulating microRNA⁃26a /FLI1 axis［J］. Bioengineered, 2021,12（1）:1212⁃1225. doi: 10.1080/21655979.2021.1907128.
［12］	Jafarinejad⁃Farsangi S, Gharibdoost F, Farazmand A, et al. MicroRNA⁃21 and microRNA⁃29a modulate the expression of collagen in dermal fibroblasts of patients with systemic sclerosis［J］. Autoimmunity, 2019,52（3）:108⁃116. doi: 10.1080/08916934. 2019.1621856.
［13］	Zhang Z, Gao X, He Y, et al. MicroRNA⁃411⁃3p inhibits bleomycin⁃induced skin fibrosis by regulating transforming growth factor⁃β/Smad ubiquitin regulatory factor⁃2 signalling［J］. J Cell Mol Med, 2021,25（24）:11290⁃11299. doi: 10.1111/jcmm. 17055.
［14］	Ghafouri⁃Fard S, Glassy MC, Abak A, et al. The interaction between miRNAs/lncRNAs and Notch pathway in human disorders［J］. Biomed Pharmacother, 2021,138:111496. doi: 10. 1016/j.biopha.2021.111496.
［15］	Wasson CW, Abignano G, Hermes H, et al. Long non⁃coding RNA HOTAIR drives EZH2⁃dependent myofibroblast activation in systemic sclerosis through miRNA 34a⁃dependent activation of NOTCH［J］. Ann Rheum Dis, 2020,79（4）:507⁃517. doi: 10. 1136/annrheumdis⁃2019⁃216542.
［16］	Wermuth PJ, Piera⁃Velazquez S, Jimenez SA. Exosomes isolated from serum of systemic sclerosis patients display alterations in their content of profibrotic and antifibrotic microRNA and induce a profibrotic phenotype in cultured normal dermal fibroblasts［J］. Clin Exp Rheumatol, 2017,35 Suppl 106（4）:21⁃30.
［17］	Li L, Zuo X, Liu D, et al. The profiles of miRNAs and lncRNAs in peripheral blood neutrophils exosomes of diffuse cutaneous systemic sclerosis［J］. J Dermatol Sci, 2020,98（2）:88⁃97. doi: 10.1016/j.jdermsci.2020.02.009.
［18］	Yao Q, Xing Y, Wang Z, et al. MiR⁃16⁃5p suppresses myofibroblast activation in systemic sclerosis by inhibiting NOTCH signaling［J］. Aging （Albany NY）, 2020,13（2）:2640⁃2654. doi: 10.18632/aging.202308.
［19］	Tsai CY, Hsieh SC, Wu TH, et al. Pathogenic roles of autoantibodies and aberrant epigenetic regulation of immune and connective tissue cells in the tissue fibrosis of patients with systemic sclerosis［J］. Int J Mol Sci, 2020,21（9）:3069. doi: 10. 3390/ijms21093069.
［20］	Henderson J, Wilkinson S, Przyborski S, et al. microRNA27a⁃3p mediates reduction of the Wnt antagonist sFRP⁃1 in systemic sclerosis［J］. Epigenetics, 2021,16（7）:808⁃817. doi: 10.1080/15592294.2020.1827715.
［21］	Henderson J, Pryzborski S, Stratton R, et al. Wnt antagonist DKK⁃1 levels in systemic sclerosis are lower in skin but not in blood and are regulated by microRNA33a⁃3p［J］. Exp Dermatol, 2021,30（1）:162⁃168. doi: 10.1111/exd.14136.
［22］	Rusek M, Michalska⁃Jakubus M, Kowal M, et al. A novel miRNA⁃4484 is up⁃regulated on microarray and associated with increased MMP⁃21 expression in serum of systemic sclerosis patients［J］. Sci Rep, 2019,9（1）:14264. doi: 10.1038/s41598⁃019⁃50695⁃y.
［23］	Malaab M, Renaud L, Takamura N, et al. Antifibrotic factor KLF4 is repressed by the miR⁃10/TFAP2A/TBX5 axis in dermal fibroblasts: insights from twins discordant for systemic sclerosis［J］. Ann Rheum Dis, 2022,81（2）:268⁃277. doi: 10.1136/annrheumdis⁃2021⁃221050.
［24］	Jin J, Ou Q, Wang Z, et al. BMSC⁃derived extracellular vesicles intervened the pathogenic changes of scleroderma in mice through miRNAs［J］. Stem Cell Res Ther, 2021,12（1）:327. doi: 10.1186/s13287⁃021⁃02400⁃y.
［25］	Rokni M, Sadeghi Shaker M, Kavosi H, et al. The role of endothelin and RAS/ERK signaling in immunopathogenesis⁃related fibrosis in patients with systemic sclerosis: an updated review with therapeutic implications［J］. Arthritis Res Ther, 2022,24（1）:108. doi: 10.1186/s13075⁃022⁃02787⁃w.
［26］	Cheng Q, Chen M, Wang H, et al. MicroRNA⁃27a⁃3p inhibits lung and skin fibrosis of systemic sclerosis by negatively regulating SPP1［J］. Genomics, 2022,114（4）:110391. doi: 10. 1016/j.ygeno.2022.110391.
［27］	Ly TD, Riedel L, Fischer B, et al. microRNA⁃145 mediates xylosyltransferase⁃I induction in myofibroblasts via suppression of transcription factor KLF4［J］. Biochem Biophys Res Commun, 2020,523（4）:1001⁃1006. doi: 10.1016/j.bbrc.2019.12.120.
［28］	Xie L, Long X, Mo M, et al. Bone marrow mesenchymal stem cell⁃derived exosomes alleviate skin fibrosis in systemic sclerosis by inhibiting the IL⁃33/ST2 axis via the delivery of microRNA⁃214［J］. Mol Immunol, 2023,157:146⁃157. doi: 10.1016/j.molimm. 2023.03.017.
［29］	Sun YH, Xie M, Wu SD, et al. Identification and interaction analysis of key genes and microRNAs in systemic sclerosis by bioinformatics approaches［J］. Curr Med Sci, 2019,39（4）:645⁃652. doi: 10.1007/s11596⁃019⁃2086⁃3.
［30］	Szabo I, Muntean L, Crisan T, et al. Novel concepts in systemic sclerosis pathogenesis: role for miRNAs［J］. Biomedicines, 2021,9（10）:1471. doi: 10.3390/biomedicines9101471.
［31］	Kozlova A, Pachera E, Maurer B, et al. Regulation of fibroblast apoptosis and proliferation by microRNA⁃125b in systemic sclerosis［J］. Arthritis Rheumatol, 2019,71（12）:2068⁃2080. doi: 10.1002/art.41041.
［32］	Bayati P, Kalantari M, Assarehzadegan MA, et al. MiR⁃27a as a diagnostic biomarker and potential therapeutic target in systemic sclerosis［J］. Sci Rep, 2022,12（1）:18932. doi: 10.1038/s41598⁃022⁃23723⁃7.
［33］	Huang Y, Luo W, Chen S, et al. Isovitexin alleviates hepatic fibrosis by regulating miR⁃21⁃mediated PI3K/Akt signaling and glutathione metabolic pathway: based on transcriptomics and metabolomics［J］. Phytomedicine, 2023,121:155117. doi: 10. 1016/j.phymed.2023.155117.
［34］	Singh N, Nagar E, Gautam A, et al. Resveratrol mitigates miR⁃212⁃3p mediated progression of diesel exhaust⁃induced pulmonary fibrosis by regulating SIRT1/FoxO3［J］. Sci Total Environ, 2023,902:166063. doi: 10.1016/j.scitotenv.2023.166063.

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微小RNA调控系统性硬皮病纤维化相关信号通路的研究进展

MicroRNAs regulating signaling pathways related to systemic scleroderma fibrosis

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