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

Abstract

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

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

References ［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.

[1]	Zhu Xue′e, Duan Manman, Ding Yuan. Long non-coding RNA-mediated competitive endogenous RNA regulatory network in keloids [J]. Chinese Journal of Dermatology, 2024, 57(7): 668-671.
[2]	Guo Lan, Jin Hongzhong. Small-molecule/biological agents in the treatment of pruritus [J]. Chinese Journal of Dermatology, 2024, 57(5): 475-478.
[3]	Yuan Liyan, Yu Xiaoling, Wang Xiaohua, Yang Bin. TYK2 inhibitors for plaque psoriasis: mechanism of action and advances in clinical research [J]. Chinese Journal of Dermatology, 2024, 0(3): 20220740-e0220740.
[4]	Liu Chenyang, Yuan Xinghua, Zhi Jiahui, Hem Kumari Rai, Lu Bo, Xu Weilu, Jin Zhehu. Effect of transmembrane protein 45A on extracellular matrix synthesis by keloid-derived fibroblasts [J]. Chinese Journal of Dermatology, 2023, 56(7): 666-669.
[5]	Liu Weizhao, Duan Zhimin, Wang Jianing, Li Min, Chen Xu, . Counteractive effect of mouse dermal fibroblasts during their adipogenic differentiation against Staphylococcus aureus infection and its mechanisms [J]. Chinese Journal of Dermatology, 2023, 56(7): 630-635.
[6]	Tang Zhiming, Jing Mengqing, Lu Lu, Shan Xiao, Zhang Cuixia, Zhang Xiaoyu, Meng Sa. Effect of Xidi Liangxue recipe on the proliferation and apoptosis of HaCaT cells through the lncRNA NEAT1/miR-485-5p/STAT3 regulatory network [J]. Chinese Journal of Dermatology, 2023, 56(7): 642-650.
[7]	Ren Fenfen, Wang Peng, Zhang Jingzhan, Kang Xiaojing. Network pharmacology-based prediction of potential effective components of traditional Chinese medicine and their molecular mechanisms of action in the anti-angiogenic treatment of Kaposi′s sarcoma [J]. Chinese Journal of Dermatology, 2023, 56(5): 428-433.
[8]	Sang Pengfei, Fang Mingsong, Li Xuan, Cao Lin, Zhao Lingling, Liu Chang, Jiang Zhiyong, Zhu Fei. Effects of the ROCK1 gene on proliferation and migration of and related molecular expression in keloid fibroblasts [J]. Chinese Journal of Dermatology, 2023, 56(3): 222-228.
[9]	Huang Wenhua, Zheng Zhenlong, Jin Zhehu. Role of transforming growth factor-β/Smad pathway and related factors in the pathogenesis of keloids [J]. Chinese Journal of Dermatology, 2023, 0(2): 20220556-e20220556.
[10]	Ding Meilin, Li Hongyang, Zhang Wei, Zeng Xuesi. Pathogenesis of extramammary Paget′s disease [J]. Chinese Journal of Dermatology, 2023, 0(2): 20220588-e20220588.
[11]	Yang Lei, Zheng Gaofeng, Chu Lei, Ran Yuping. Mas-related G protein-coupled rceptor X2 in itch in atopic dermatitis [J]. Chinese Journal of Dermatology, 2023, 0(2): 20230078-e0230078.
[12]	Yang Yaqi, Jiang Xin, Chang Jinxiu, Tu Ying, Ma Yanyun, He Li, Gu Hua. Effect of blue light on the biological activity of human skin keratinocytes, fibroblasts and melanocytes: a preliminary study [J]. Chinese Journal of Dermatology, 2023, 56(12): 1115-1122.
[13]	Qiao Jiaxi, Chen Yao, Du Kun, Chen Liuqing, Chen Jinbo, Wei Li. A preliminary study on the inhibitory effect of gallic acid on the growth of human keloid fibroblasts by the transforming growth factor-β/Sma- and Mad-related proteins signaling pathway [J]. Chinese Journal of Dermatology, 2023, 56(12): 1138-1145.
[14]	Gong Chunxiang, Shao Xin, Fan Qinhe. Clinical and pathological analysis of 19 patients with superficial CD34-positive fibroblastic tumor [J]. Chinese Journal of Dermatology, 2023, 56(12): 1158-1162.
[15]	Lu Nan, Tan Xingyou, Liu Xiang, Niu Lili, Yao Shulan. Association of single nucleotide polymorphisms in microRNAs with the risk of chronic spontaneous urticaria [J]. Chinese Journal of Dermatology, 2022, 55(9): 806-809.

MicroRNAs regulating signaling pathways related to systemic scleroderma fibrosis

PDF

PDF (Mobile)

Knowledge

Abstract

Cite this article

share this article

References ［34］

Related Articles 15

Metrics

Comments

Recommended 10