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Regulation of gene expression by miRNA-455-3p, upregulated in the conjunctival epithelium of patients with Stevens-Johnson syndrome in the chronic stage.
Sci Rep. 2020 10 14; 10(1):17239.SR

Abstract

To investigate the role of miRNA in the pathogenesis underlying ocular surface complications in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in the chronic stage. Using oligonucleotide microarrays, we performed comprehensive miRNA analysis of the conjunctival epithelium of SJS/TEN patients with severe ocular complications (SOC) in the chronic stage (n = 3). Conjunctival epithelium of patients with conjunctival chalasis (n = 3) served as the control. We confirmed the down- and up-regulation of miRNA of interest by quantitative real-time polymerase chain reaction (RT-PCR) assays using the conjunctival epithelium from 6 SJS/TEN with SOC patients and 7 controls. We focused on miRNA-455-3p, which is significantly upregulated in the conjunctival epithelium of the SJS/TEN patients, and investigated its function by inhibiting miR-455-3p in primary human conjunctival epithelial cells (PHCjEs). Comprehensive miRNA expression analysis showed that the expression of 5 kinds of miRNA was up-regulated more than fivefold, and that the expression of another 5 kinds of miRNA was down-regulated by less than one-fifth. There was a significant difference between the SJS/TEN patients and the controls [analysis of variance (ANOVA) p < 0.05]. Quantitative miRNA PCR assay showed that hsa-miR-31* and hsa-miR-455-3p were significantly up-regulated in the conjunctival epithelium of the SJS/TEN patients. Comprehensive gene expression analysis of PHCjEs transfected with the hsa-miR-455-3p inhibitor and quantitative RT PCR assay showed that ANKRD1, CXCL8, CXCL2, GEM, PTGS2, RNASE8, IL6, and CXCL1 were down-regulated by the hsa-miR-455-3p inhibitor. Quantitative RT-PCR, focused on the genes that tended to be up-regulated in SJS/TEN with SOC, revealed that the expression of IL1A, KPRP, IL36G, PPP1R3C, and ADM was significantly down-regulated in PHCjEs transfected with the hsa-miR-455-3p inhibitor. Our results suggest that miRNA-455-3p could regulate many genes including innate immune related genes in human conjunctival epithelium, and that its up-regulation contributes to the pathogenesis on the ocular surface in SJS/TEN patients with the SOC in the chronic stage. Our findings may lead to the development of new treatments using the miRNA-455-3p inhibitor.

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Authors+Show Affiliations

Ueta M
Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji, Kawaramachi, Kamigyoku, Kyoto, 602-0841, Japan. mueta@koto.kpu-m.ac.jp.
Nishigaki H
Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji, Kawaramachi, Kamigyoku, Kyoto, 602-0841, Japan.
Sotozono C
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yokoi N
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Mizushima K
Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Naito Y
Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kinoshita S
Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji, Kawaramachi, Kamigyoku, Kyoto, 602-0841, Japan.

MeSH

AdultChemokine CXCL2ConjunctivaEpitheliumHumansInterleukin-8MicroRNAsMiddle AgedMuscle ProteinsNuclear ProteinsRepressor ProteinsStevens-Johnson Syndrome

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33057072

Citation

Ueta, Mayumi, et al. "Regulation of Gene Expression By miRNA-455-3p, Upregulated in the Conjunctival Epithelium of Patients With Stevens-Johnson Syndrome in the Chronic Stage." Scientific Reports, vol. 10, no. 1, 2020, p. 17239.
Ueta M, Nishigaki H, Sotozono C, et al. Regulation of gene expression by miRNA-455-3p, upregulated in the conjunctival epithelium of patients with Stevens-Johnson syndrome in the chronic stage. Sci Rep. 2020;10(1):17239.
Ueta, M., Nishigaki, H., Sotozono, C., Yokoi, N., Mizushima, K., Naito, Y., & Kinoshita, S. (2020). Regulation of gene expression by miRNA-455-3p, upregulated in the conjunctival epithelium of patients with Stevens-Johnson syndrome in the chronic stage. Scientific Reports, 10(1), 17239. https://doi.org/10.1038/s41598-020-74211-9
Ueta M, et al. Regulation of Gene Expression By miRNA-455-3p, Upregulated in the Conjunctival Epithelium of Patients With Stevens-Johnson Syndrome in the Chronic Stage. Sci Rep. 2020 10 14;10(1):17239. PubMed PMID: 33057072.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of gene expression by miRNA-455-3p, upregulated in the conjunctival epithelium of patients with Stevens-Johnson syndrome in the chronic stage. AU - Ueta,Mayumi, AU - Nishigaki,Hiromi, AU - Sotozono,Chie, AU - Yokoi,Norihiko, AU - Mizushima,Katsura, AU - Naito,Yuji, AU - Kinoshita,Shigeru, Y1 - 2020/10/14/ PY - 2020/06/30/received PY - 2020/09/02/accepted PY - 2020/10/15/entrez PY - 2020/10/16/pubmed PY - 2021/3/10/medline SP - 17239 EP - 17239 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - To investigate the role of miRNA in the pathogenesis underlying ocular surface complications in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) in the chronic stage. Using oligonucleotide microarrays, we performed comprehensive miRNA analysis of the conjunctival epithelium of SJS/TEN patients with severe ocular complications (SOC) in the chronic stage (n = 3). Conjunctival epithelium of patients with conjunctival chalasis (n = 3) served as the control. We confirmed the down- and up-regulation of miRNA of interest by quantitative real-time polymerase chain reaction (RT-PCR) assays using the conjunctival epithelium from 6 SJS/TEN with SOC patients and 7 controls. We focused on miRNA-455-3p, which is significantly upregulated in the conjunctival epithelium of the SJS/TEN patients, and investigated its function by inhibiting miR-455-3p in primary human conjunctival epithelial cells (PHCjEs). Comprehensive miRNA expression analysis showed that the expression of 5 kinds of miRNA was up-regulated more than fivefold, and that the expression of another 5 kinds of miRNA was down-regulated by less than one-fifth. There was a significant difference between the SJS/TEN patients and the controls [analysis of variance (ANOVA) p < 0.05]. Quantitative miRNA PCR assay showed that hsa-miR-31* and hsa-miR-455-3p were significantly up-regulated in the conjunctival epithelium of the SJS/TEN patients. Comprehensive gene expression analysis of PHCjEs transfected with the hsa-miR-455-3p inhibitor and quantitative RT PCR assay showed that ANKRD1, CXCL8, CXCL2, GEM, PTGS2, RNASE8, IL6, and CXCL1 were down-regulated by the hsa-miR-455-3p inhibitor. Quantitative RT-PCR, focused on the genes that tended to be up-regulated in SJS/TEN with SOC, revealed that the expression of IL1A, KPRP, IL36G, PPP1R3C, and ADM was significantly down-regulated in PHCjEs transfected with the hsa-miR-455-3p inhibitor. Our results suggest that miRNA-455-3p could regulate many genes including innate immune related genes in human conjunctival epithelium, and that its up-regulation contributes to the pathogenesis on the ocular surface in SJS/TEN patients with the SOC in the chronic stage. Our findings may lead to the development of new treatments using the miRNA-455-3p inhibitor. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/33057072/Regulation_of_gene_expression_by_miRNA_455_3p_upregulated_in_the_conjunctival_epithelium_of_patients_with_Stevens_Johnson_syndrome_in_the_chronic_stage_ DB - PRIME DP - Unbound Medicine ER -