Academic Journal
Targeting the RNA acetyltransferase NAT10 attenuates pulmonary fibrosis via the ac4C-mediated regulation of the C/EBPβ-ITGA11 axis.
| Τίτλος: | Targeting the RNA acetyltransferase NAT10 attenuates pulmonary fibrosis via the ac4C-mediated regulation of the C/EBPβ-ITGA11 axis. |
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| Συγγραφείς: | Wang Z; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Wu Q; Department of Respiratory and Critical Care Medicine, Jinling Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Yao Y; Department of Pulmonary and Critical Care Medicine, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, China., Cao M; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Ding J; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Xiao Y; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Huang X; Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China; School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: huangxm2017@pku.edu.cn., Luo J; Department of Cardiothoracic Surgery, Jinling Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: luojing_2767983@163.com. |
| Πηγή: | International immunopharmacology [Int Immunopharmacol] 2026 Jul 15; Vol. 181, pp. 116793. Date of Electronic Publication: 2026 May 05. |
| 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): | CCAAT-Enhancer-Binding Protein-beta*/metabolism , CCAAT-Enhancer-Binding Protein-beta*/genetics , Idiopathic Pulmonary Fibrosis*/drug therapy , Idiopathic Pulmonary Fibrosis*/pathology , Idiopathic Pulmonary Fibrosis*/metabolism , N-Terminal Acetyltransferase E*/metabolism , N-Terminal Acetyltransferase E*/antagonists & inhibitors , N-Terminal Acetyltransferase E*/genetics , Integrin alpha Chains*/metabolism , Integrin alpha Chains*/genetics, Fibroblasts/drug effects ; Lung/pathology ; Lung/drug effects ; Cytidine/metabolism ; Cytidine/analogs & derivatives ; Animals ; Humans ; Bleomycin ; Mice ; Mice, Inbred C57BL ; Male ; Pulmonary Fibrosis ; Benzoates ; Nitrobenzenes ; Pyrazolones ; N-Terminal Acetyltransferases |
| Περίληψη: | Identifying novel therapeutic targets is urgent for idiopathic pulmonary fibrosis (IPF), a fatal disease with limited treatment options. N-acetyltransferase 10 (NAT10), the sole enzyme responsible for RNA N4-acetylcytidine (ac4C) modification, is implicated in diverse pathological processes. This study aimed to validate NAT10 as a potential therapeutic target for pulmonary fibrosis by utilizing the established small-molecule inhibitor, Remodelin, to functionally interrogate its role. We observed that NAT10 was significantly upregulated in lung tissues from IPF patients and bleomycin (BLM)-treated mice. Pharmacological blockade of NAT10 activity using Remodelin significantly attenuated lung structural destruction and collagen deposition in vivo. In vitro, inhibiting NAT10 function suppressed fibroblast activation and extracellular matrix production. Mechanistically, rather than directly modifying effector molecules, NAT10 stabilized the mRNA of transcription factor C/EBPβ via ac4C modification. This stabilization led to the transcriptional upregulation of Integrin α11 (ITGA11), thereby promoting fibroblast activation. Rescue experiments confirmed that the pro-fibrotic effects of NAT10 are dependent on this C/EBPβ-ITGA11 axis via its acetyltransferase activity. Collectively, our findings characterize NAT10 as a key pathogenic driver and demonstrate that inhibition of this epigenetic regulator offers a promising therapeutic strategy for ameliorating pulmonary fibrosis. (Copyright © 2026 The Authors. Published by 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: C/EBPβ; Fibroblast activation; ITGA11; NAT10; Pulmonary fibrosis; ac4C |
| Substance Nomenclature: | 0 (CCAAT-Enhancer-Binding Protein-beta) 11056-06-7 (Bleomycin) EC 2.3.1.258 (N-Terminal Acetyltransferase E) EC 2.3.1.88 (NAT10 protein, human) 0 (Integrin alpha Chains) 0 (4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid) 5CSZ8459RP (Cytidine) 0 (Benzoates) 0 (Nitrobenzenes) 0 (Pyrazolones) EC 2.3.1.88 (N-Terminal Acetyltransferases) |
| Entry Date(s): | Date Created: 20260506 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260716 |
| DOI: | 10.1016/j.intimp.2026.116793 |
| PMID: | 42090905 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2026.116793 |