Academic Journal
A novel LncRNA TUG1/miR-30d/e-3p/SNAI2 ceRNA axis drives dermal fibrosis in systemic sclerosis via direct transcriptional activation of COL1A1.
| Τίτλος: | A novel LncRNA TUG1/miR-30d/e-3p/SNAI2 ceRNA axis drives dermal fibrosis in systemic sclerosis via direct transcriptional activation of COL1A1. |
|---|---|
| Συγγραφείς: | Zhu R; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Xiao Y; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China; Department of Gynaecology and Obstetrics, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Clinical Nursing Teaching and Research Section, the Second Xiangya Hospital of Central South University, Changsha, Hunan, China., Liu L; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Chai K; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Gong H; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Wei Y; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Tang Z; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Song Z; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Liu J; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Shi Y; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Zeng Z; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China., Xiao R; Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Clinical Medical Research Center of Major Skin Diseases and Skin Health of Hunan Province, Changsha, China; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China. Electronic address: xiaorong65@csu.edu.cn., Pi Z; Clinical Medical Research Center for Systemic Autoimmune Diseases in Hunan Province, China; Department of Medical Genetics, Second Xiangya Hospita, Central South University, Changsha, Hunan, China. Electronic address: pizixin0525@csu.edu.cn. |
| Πηγή: | International immunopharmacology [Int Immunopharmacol] 2026 Oct 15; Vol. 187, pp. 117232. Date of Electronic Publication: 2026 Aug 10. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| Ιατρικοί όροι (MeSH): | RNA, Long Noncoding*/genetics , RNA, Long Noncoding*/metabolism , Scleroderma, Systemic*/genetics , Scleroderma, Systemic*/pathology , Scleroderma, Systemic*/metabolism , MicroRNAs*/genetics , MicroRNAs*/metabolism , Snail Family Transcription Factors*/genetics , Snail Family Transcription Factors*/metabolism , Collagen Type I*/genetics , Collagen Type I*/metabolism , Skin*/pathology, Fibroblasts/metabolism ; Fibroblasts/pathology ; Animals ; Humans ; Fibrosis ; Collagen Type I, alpha 1 Chain ; Bleomycin ; Mice ; RNA, Competitive Endogenous ; Transcriptional Activation ; Disease Models, Animal ; Cells, Cultured ; Male ; Mice, Inbred C57BL |
| Περίληψη: | Systemic sclerosis (SSc) is a severe autoimmune disease characterized by progressive dermal fibrosis, aberrant fibroblast activation, and excessive collagen deposition. Although noncoding RNA-mediated regulation has been increasingly implicated in fibrotic diseases, the role of the long noncoding RNA taurine-upregulated gene 1 (TUG1) in SSc-associated skin fibrosis remains unclear. In this study, we investigated the function and mechanism of TUG1 in primary dermal fibroblasts isolated from lesional skin of patients with SSc and in a bleomycin-induced mouse model of dermal fibrosis. TUG1 expression was significantly increased in SSc dermal fibroblasts. Functional assays showed that TUG1 promoted fibroblast proliferation, migration, and COL1A1 expression, whereas TUG1 silencing attenuated these profibrotic phenotypes. Mechanistically, TUG1 acted as a competing endogenous RNA by sponging miR-30d-3p and miR-30e-3p, thereby relieving their repression of the transcription factor SNAI2. SNAI2 directly bound to the COL1A1 promoter and activated its transcription. In vivo, Tug1 knockdown alleviated bleomycin-induced dermal fibrosis, increased miR-30d-3p/miR-30e-3p levels, and reduced SNAI2 expression and collagen deposition. These findings identify the TUG1-miR-30d-3p/miR-30e-3p-SNAI2-COL1A1 axis as a potential therapeutic target in SSc skin fibrosis. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Competing endogenous RNA; Dermal fibrosis; SNAI2; Systemic sclerosis; TUG1; miR-30 family |
| Substance Nomenclature: | 0 (RNA, Long Noncoding) 0 (MicroRNAs) 0 (Snail Family Transcription Factors) 0 (Collagen Type I) 0 (Collagen Type I, alpha 1 Chain) 11056-06-7 (Bleomycin) 0 (RNA, Competitive Endogenous) 0 (TUG1 long noncoding RNA, human) 0 (Mirn30d microRNA, mouse) 0 (long non-coding RNA TUG1, mouse) |
| Entry Date(s): | Date Created: 20260810 Date Completed: 20260911 Latest Revision: 20260911 |
| Update Code: | 20260912 |
| DOI: | 10.1016/j.intimp.2026.117232 |
| PMID: | 42574808 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1878-1705 |
|---|---|
| DOI: | 10.1016/j.intimp.2026.117232 |