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01-12-2021 | Atopic Dermatitis | Original Paper

Dysregulated microRNA expression in IL-4 transgenic mice, an animal model of atopic dermatitis

Authors: Lei Bao, Cecilia S. Chau, Zhengdeng Lei, Hong Hu, Angelina G. Chan, Kyle T. Amber, Mark Maienschein-Cline, Maria M. Tsoukas

Published in: Archives of Dermatological Research | Issue 10/2021

Abstract

IL-4 plays an important role in the pathogenesis of atopic dermatitis (AD). Previously we showed that the expression of genes in chemotaxis, angiogenesis, inflammation and barrier functions is dysregulated in IL-4 transgenic (Tg) mice, a well-characterized AD mouse model. In this study, we aim to study differential expression of microRNAs in IL-4 Tg mice. As compared with wild-type mice, we found that 10 and 79 microRNAs are dysregulated in the skin of IL-4 mice before and after the onset of skin lesions, respectively. Bioinformatic analysis and previous reports show that these dysregulated microRNAs may be involved in the NF-κB, TLRs, IL-4/IL-13, MAPK and other pathways. We also found that miR-139-5p and miR-196b-3p are significantly up-regulated in the peripheral blood of IL-4 Tg mice. Taken together, our data have identified many dysregulated microRNAs in IL-4 Tg mice, which may play important roles in AD pathogenesis and pathophysiology.

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Aggarwal BB, Shishodia S, Takada Y, Jackson-Bernitsas D, Ahn KS, Sethi G, Ichikawa H (2005) TNF blockade: an inflammatory issue. In: Numerof R, Dinarello CA, Asadullah K (eds) Cytokines as potential therapeutic targets for inflammatory skin diseases. Ernst Schering Research Foundation Workshop, vol 56. Springer, Berlin, Heidelberg, pp 161–186. https://doi.org/10.1007/3-540-37673-9_10CrossRef

Bao L, Alexander JB, Shi VY, Mohan GC, Chan LS (2014) Interleukin-4 up-regulation of epidermal interleukin-19 expression in keratinocytes involves the binding of signal transducer and activator of transcription 6 (Stat6) to the imperfect Stat6 sites. Immunology 143:601–608. https://doi.org/10.1111/imm.12339CrossRefPubMedPubMedCentral

Bao L, Alexander JB, Zhang H, Shen K, Chan LS (2016) Interleukin-4 downregulation of involucrin expression in human epidermal keratinocytes involves stat6 sequestration of the coactivator CREB-binding protein. J Interferon Cytokine Res 36:374–381. https://doi.org/10.1089/jir.2015.0056CrossRefPubMedPubMedCentral

Bao L, Chau C, Bao J, Tsoukas MM, Chan LS (2018) IL-4 dysregulates microRNAs involved in inflammation, angiogenesis and apoptosis in epidermal keratinocytes. Microbiol Immunol 62:732–736. https://doi.org/10.1111/1348-0421.12650CrossRefPubMed

Bao L, Mohan GC, Alexander JB, Doo C, Shen K, Bao J, Chan LS (2017) A molecular mechanism for IL-4 suppression of loricrin transcription in epidermal keratinocytes: implication for atopic dermatitis pathogenesis. Innate Immun 23:641–647. https://doi.org/10.1177/1753425917732823CrossRefPubMed

Bao L, Zhang H, Mohan GC, Shen K, Chan LS (2016) Differential expression of inflammation-related genes in IL-4 transgenic mice before and after the onset of atopic dermatitis skin lesions. Mol Cell Probes 30:30–38. https://doi.org/10.1016/j.mcp.2015.11.001CrossRefPubMed

Barry ZR, Kynast RW, Stinson WA, Fox DA, Amin MA, Rabquer BJ (2016) miR429 is Upregulated in inflammatory monocytes and regulates monocyte migration. Faseb J. https://doi.org/10.1096/fasebj.30.1_supplement.1028.13CrossRef

Biton M, Levin A, Slyper M, Alkalay I, Horwitz E, Mor H, Kredo-Russo S, Avnit-Sagi T, Cojocaru G, Zreik F, Bentwich Z, Poy MN, Artis D, Walker MD, Hornstein E, Pikarsky E, Ben-Neriah Y (2011) Epithelial microRNAs regulate gut mucosal immunity via epithelium-T cell crosstalk. Nat Immunol 12:239-U275. https://doi.org/10.1038/ni.1994CrossRefPubMed

Chan LS, Robinson N, Xu L (2001) Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. J Invest Dermatol 117:977–983. https://doi.org/10.1046/j.0022-202x.2001.01484.xCrossRefPubMed

10.

Chiba Y, Tanabe M, Goto K, Sakai H, Misawa M (2009) Down-regulation of miR-133a contributes to up-regulation of Rhoa in bronchial smooth muscle cells. Am J Respir Crit Care Med 180:713–719. https://doi.org/10.1164/rccm.200903-0325OCCrossRefPubMed

11.

Chuang TD, Ho M, Khorram O (2015) The regulatory function of miR-200c on inflammatory and cell-cycle associated genes in SK-LMS-1, a leiomyosarcoma cell line. Reprod Sci 22:563–571. https://doi.org/10.1177/1933719114553450CrossRefPubMed

12.

da Silva W, dos Santos RA, Moraes KC (2016) Mir-351-5p contributes to the establishment of a pro-inflammatory environment in the H9c2 cell line by repressing PTEN expression. Mol Cell Biochem 411:363–371. https://doi.org/10.1007/s11010-015-2598-5CrossRefPubMed

13.

Gandhi NA, Pirozzi G, Graham NMH (2017) Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol 13:425–437. https://doi.org/10.1080/1744666X.2017.1298443CrossRefPubMed

14.

Guidi R, Wedeles CJ, Wilson MS (2020) ncRNAs in type-2 immunity. Non-Coding RNA 6:10 (ARTN103390/ncrna6010010)CrossRef

15.

Hu J, Zhai C, Hu J, Li Z, Fei H, Wang Z, Fan W (2017) MiR-23a inhibited IL-17-mediated proinflammatory mediators expression via targeting IKKalpha in articular chondrocytes. Int Immunopharmacol 43:1–6. https://doi.org/10.1016/j.intimp.2016.11.031CrossRefPubMed

16.

Hu YW, Zhao JY, Li SF, Huang JL, Qiu YR, Ma X, Wu SG, Chen ZP, Hu YR, Yang JY, Wang YC, Gao JJ, Sha YH, Zheng L, Wang Q (2015) RP5-833A20.1/miR-382-5p/NFIA-dependent signal transduction pathway contributes to the regulation of cholesterol homeostasis and inflammatory reaction. Arterioscler Thromb Vasc Biol 35:87–101. https://doi.org/10.1161/ATVBAHA.114.304296CrossRefPubMed

17.

Huang J, Zhu L, Qiu C, Xu X, Zhang L, Ding X, Liao Q, Xu J, Zhang X (2017) MicroRNA miR-126-5p enhances the inflammatory responses of monocytes to lipopolysaccharide stimulation by suppressing cylindromatosis in chronic HIV-1 infection. J Virol. https://doi.org/10.1128/JVI.02048-16CrossRefPubMedPubMedCentral

18.

Jeong JH, Park SJ, Dickinson SI, Luo JL (2017) A constitutive intrinsic inflammatory signaling circuit composed of miR-196b, Meis2, PPP3CC, and p65 drives prostate cancer castration resistance. Mol Cell 65:154–167. https://doi.org/10.1016/j.molcel.2016.11.034CrossRefPubMed

19.

Jin HL, He R, Oyoshi M, Geha RS (2009) Animal models of atopic dermatitis. J Invest Dermatol 129:31–40. https://doi.org/10.1038/jid.2008.106CrossRefPubMedPubMedCentral

20.

Liu Z, Jiang J, Yang Q, Xiong Y, Zou D, Yang C, Xu J, Zhan H (2016) MicroRNA-682-mediated downregulation of PTEN in intestinal epithelial cells ameliorates intestinal ischemia-reperfusion injury. Cell Death Dis 7:e2210. https://doi.org/10.1038/cddis.2016.84CrossRefPubMedPubMedCentral

21.

Lu TX, Hartner J, Lim EJ, Fabry V, Mingler MK, Cole ET, Orkin SH, Aronow BJ, Rothenberg ME (2011) MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J Immunol 187:3362–3373. https://doi.org/10.4049/jimmunol.1101235CrossRefPubMed

22.

Mun J, Tam C, Chan G, Kim JH, Evans D, Fleiszig S (2013) MicroRNA-762 is upregulated in human corneal epithelial cells in response to tear fluid and pseudomonas aeruginosa antigens and negatively regulates the expression of host defense genes encoding RNase7 and ST2. PLoS ONE 8:e57850. https://doi.org/10.1371/journal.pone.0057850CrossRefPubMedPubMedCentral

23.

Otsuka A, Nomura T, Rerknimitr P, Seidel JA, Honda T, Kabashima K (2017) The interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis. Immunol Rev 278:246–262. https://doi.org/10.1111/imr.12545CrossRefPubMed

24.

Shao Y, Lv C, Wu C, Zhou Y, Wang Q (2016) Mir-217 promotes inflammation and fibrosis in high glucose cultured rat glomerular mesangial cells via Sirt1/HIF-1alpha signaling pathway. Diabetes Metab Res Rev 32:534–543. https://doi.org/10.1002/dmrr.2788CrossRefPubMed

25.

Shi VY, Bao L, Chan LS (2012) Inflammation-driven dermal lymphangiogenesis in atopic dermatitis is associated with CD11b+ macrophage recruitment and VEGF-C up-regulation in the IL-4-transgenic mouse model. Microcirculation 19:567–579. https://doi.org/10.1111/j.1549-8719.2012.00189.xCrossRefPubMed

26.

Simpson LJ, Patel S, Bhakta NR, Choy DF, Brightbill HD, Ren X, Wang YL, Pua HH, Baumjohann D, Montoya MM, Panduro M, Remedios KA, Huang XZ, Fahy JV, Arron JR, Woodruff PG, Ansel KM (2014) A microRNA upregulated in asthma airway T cells promotes T(H)2 cytokine production. Nat Immunol 15:1162–1170. https://doi.org/10.1038/ni.3026CrossRefPubMedPubMedCentral

27.

Song L, Lin C, Gong H, Wang C, Liu L, Wu J, Tao S, Hu B, Cheng SY, Li M, Li J (2013) miR-486 sustains NF-kappaB activity by disrupting multiple NF-kappaB-negative feedback loops. Cell Res 23:274–289. https://doi.org/10.1038/cr.2012.174CrossRefPubMed

28.

Su S, Zhao Q, He C, Huang D, Liu J, Chen F, Chen J, Liao JY, Cui X, Zeng Y, Yao H, Su F, Liu Q, Jiang S, Song E (2015) miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program. Nat Commun 6:8523. https://doi.org/10.1038/ncomms9523CrossRefPubMed

29.

Tamai K, Kaneda Y, Nakamura H, Aoki M, Morishita R, Hashimoto K, Morita A, Katayama I, Hanada K (2005) NFkappaB decoy DNA for treatment of atopic dermatitis. Nihon Rinsho 63(Suppl 12):659–663PubMed

30.

Tenda Y, Yamashita M, Kimura MY, Hasegawa A, Shimizu C, Kitajima M, Onodera A, Suzuki A, Seki N, Nakayama T (2006) Hyperresponsive TH2 cells with enhanced nuclear factor-kappa B activation induce atopic dermatitis-like skin lesions in Nishiki-nezumi Cinnamon/Nagoya mice. J Allergy Clin Immunol 118:725–733. https://doi.org/10.1016/j.jaci.2006.05.024CrossRefPubMed

31.

Tokuhira N, Kitagishi Y, Suzuki M, Minami A, Nakanishi A, Ono Y, Kobayashi K, Matsuda S, Ogura Y (2015) PI3K/AKT/PTEN pathway as a target for Crohn’s disease therapy. Int J Mol Med 35:10–16. https://doi.org/10.3892/ijmm.2014.1981CrossRefPubMed

32.

Wang Y, Weng H, Song JF, Deng YH, Li S, Liu HB (2017) Activation of the HMGB1-TLR4-NF-kappa B pathway may occur in patients with atopic eczema. Mol Med Rep 16:2714–2720. https://doi.org/10.3892/mmr.2017.6942CrossRefPubMedPubMedCentral

33.

Wardyn JD, Ponsford AH, Sanderson CM (2015) Dissecting molecular cross-talk between Nrf2 and NF-kappa B response pathways. Biochem Soc T 43:621–626. https://doi.org/10.1042/Bst20150014CrossRef

34.

Wei Y, Nazari-Jahantigh M, Chan L, Zhu M, Heyll K, Corbalan-Campos J, Hartmann P, Thiemann A, Weber C, Schober A (2013) The microRNA-342-5p fosters inflammatory macrophage activation through an Akt1- and microRNA-155-dependent pathway during atherosclerosis. Circulation 127:1609–1619. https://doi.org/10.1161/CIRCULATIONAHA.112.000736CrossRefPubMed

35.

Xiaokelaiti H, Zhi X, Yusufujiang Y, Aikebaier A (2016) MiR-128-3p regulates inflammatory response in LPS-stimulated macrophages through the TLR4-NF-kappa B pathway. Int J Clin Exp Med 9:8005–8013

36.

Xie W, Lu Q, Wang K, Lu J, Gu X, Zhu D, Liu F, Guo Z (2018) miR-34b-5p inhibition attenuates lung inflammation and apoptosis in an LPS-induced acute lung injury mouse model by targeting progranulin. J Cell Physiol 233:6615–6631. https://doi.org/10.1002/jcp.26274CrossRefPubMedPubMedCentral

37.

Yang JC, Wu SC, Rau CS, Chen YC, Lu TH, Wu YC, Tzeng SL, Wu CJ, Hsieh CH (2015) TLR4/NF-kappaB-responsive microRNAs and their potential target genes: a mouse model of skeletal muscle ischemia-reperfusion injury. Biomed Res Int 2015:410721. https://doi.org/10.1155/2015/410721CrossRefPubMedPubMedCentral

38.

Yang Y, Wang Y, Liang Q, Yao L, Gu S, Bai X (2017) MiR-338-5p promotes inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis via targeting SPRY1. J Cell Biochem 118:2295–2301. https://doi.org/10.1002/jcb.25883CrossRefPubMed

39.

Yang Z, Zhong LN, Zhong SC, Xian RH, Yuan BQ (2015) miR-203 protects microglia mediated brain injury by regulating inflammatory responses via feedback to MyD88 in ischemia. Mol Immunol 65:293–301. https://doi.org/10.1016/j.molimm.2015.01.019CrossRefPubMed

40.

Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004) Modulation of NF-kappa B-dependent transcription and cell survival by the SIRT1 deacetylase. Embo J 23:2369–2380. https://doi.org/10.1038/sj.emboj.7600244CrossRefPubMedPubMedCentral

41.

Ying HJ, Kang YH, Zhang H, Zhao DJ, Xia JY, Lu Z, Wang HH, Xu F, Shi LY (2015) MiR-127 modulates macrophage polarization and promotes lung inflammation and injury by activating the JNK pathway. J Immunol 194:1239–1251. https://doi.org/10.4049/jimmunol.1402088CrossRefPubMed

42.

Yu X, Wang MF, Li LF, Zhang L, Chan MTV, Wu WKK (2020) MicroRNAs in atopic dermatitis: a systematic review. J Cell Mol Med 24:5966–5972. https://doi.org/10.1111/jcmm.15208CrossRefPubMedPubMedCentral

43.

Zhao D, Zhuang N, Ding Y, Kang Y, Shi L (2016) MiR-221 activates the NF-kappaB pathway by targeting A20. Biochem Biophys Res Commun 472:11–18. https://doi.org/10.1016/j.bbrc.2015.11.009CrossRefPubMed

44.

Zhao JJ, Hu YW, Huang C, Ma X, Kang CM, Zhang Y, Guo FX, Lu JB, Xiu JC, Qiu YR, Sha YH, Gao JJ, Wang YC, Li P, Xu BM, Zheng L, Wang Q (2016) Dihydrocapsaicin suppresses proinflammatory cytokines expression by enhancing nuclear factor IA in a NF-kappaB-dependent manner. Arch Biochem Biophys 604:27–35. https://doi.org/10.1016/j.abb.2016.06.002CrossRefPubMed

45.

Zhao XJ, Yu HW, Yang YZ, Wu WY, Chen TY, Jia KK, Kang LL, Jiao RQ, Kong LD (2018) Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway. Redox Biol 18:124–137. https://doi.org/10.1016/j.redox.2018.07.002CrossRefPubMedPubMedCentral

46.

Zhou Y, Yang Q, Xu H, Zhang J, Deng H, Gao H, Yang J, Zhao D, Liu F (2016) miRNA-221-3p enhances the secretion of interleukin-4 in mast cells through the phosphatase and tensin homolog/p38/nuclear factor-kappab pathway. PLoS ONE 11:e0148821. https://doi.org/10.1371/journal.pone.0148821CrossRefPubMedPubMedCentral

47.

Zhu B, Ye J, Nie Y, Ashraf U, Zohaib A, Duan X, Fu ZF, Song Y, Chen H, Cao S (2015) MicroRNA-15b modulates Japanese encephalitis virus-mediated inflammation via targeting RNF125. J Immunol 195:2251–2262. https://doi.org/10.4049/jimmunol.1500370CrossRefPubMed

Title: Dysregulated microRNA expression in IL-4 transgenic mice, an animal model of atopic dermatitis
Authors: Lei Bao
Cecilia S. Chau
Zhengdeng Lei
Hong Hu
Angelina G. Chan
Kyle T. Amber
Mark Maienschein-Cline
Maria M. Tsoukas
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keyword: Atopic Dermatitis
Published in: Archives of Dermatological Research / Issue 10/2021
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-020-02176-w

2024 ASCO Annual Meeting

Springer Medicine

Dysregulated microRNA expression in IL-4 transgenic mice, an animal model of atopic dermatitis

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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