Academic Journal
RNA-binding protein RBM47 promotes endothelial-to-mesenchymal transition and neointimal hyperplasia in arteriovenous fistulas.
| Τίτλος: | RNA-binding protein RBM47 promotes endothelial-to-mesenchymal transition and neointimal hyperplasia in arteriovenous fistulas. |
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| Συγγραφείς: | Li Z; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China., Lan X; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China., Zhang C; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China., Hu T; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China., Yao S; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China., Zhao Y; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China., Yu X; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China., Sun X; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China., Ma H; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China., Wang Q; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.; Department of Nephrology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, 518055, China., Liang H; Department of Clinical Pharmacology (The Heilongjiang Key Laboratory of Drug Research), Harbin Medical University, Harbin, 150086, China., Jiao J; Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. jiaojundong@163.com.; Institute of Nephrology, Harbin Medical University, Harbin, 150086, China. jiaojundong@163.com. |
| Πηγή: | BMC nephrology [BMC Nephrol] 2026 Jul 10; Vol. 27 (1). Date of Electronic Publication: 2026 Jul 10. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: BioMed Central Country of Publication: England NLM ID: 100967793 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2369 (Electronic) Linking ISSN: 14712369 NLM ISO Abbreviation: BMC Nephrol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : BioMed Central, [2000- |
| Ιατρικοί όροι (MeSH): | Neointima*/pathology , Neointima*/metabolism , Neointima*/genetics , RNA-Binding Proteins*/genetics , RNA-Binding Proteins*/metabolism , Endothelial-Mesenchymal Transition*/genetics , Arteriovenous Shunt, Surgical*/adverse effects, Animals ; Humans ; Hyperplasia ; Mice ; Male |
| Περίληψη: | Background: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis in patients with end-stage renal disease. However, AVF stenosis, a severe complication, significantly impairs the patient's quality of life. The mechanisms underlying AVF stenosis are multifactorial, with neointima (NI) hyperplasia within the fistula being a key contributor. While the involvement of RNA-binding proteins in the pathogenesis of various vascular diseases has garnered increasing attention, their role in autogenous AVFs remains poorly understood. Methods: Differentially expressed genes in a mouse AVF model were identified through public database analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed RBM47 as the most significantly altered gene. Endothelial-specific RBM47 overexpression was achieved by local delivery of adeno-associated virus (AAV)-RBM47 using F127 hydrogel. Hematoxylin-eosin staining was used to assess neointimal thickness in human and mouse AVF tissues. RBM47 expression and function were evaluated by qRT-PCR, Western blotting, and assays of proliferation and migration. Mechanistic studies, including transcriptome sequencing, Replicate Multivariate Analysis of Transcript Splicing (rMATS) analysis, RNA-Binding Protein Immunoprecipitation (RIP) Assay, molecular docking, immunohistochemistry, and immunofluorescence, were performed to investigate the relationship between RBM47, SEC31A splicing, and downstream signaling. Results: RBM47 expression was markedly increased in stenotic AVF tissues from both patients and mouse models. Endothelial overexpression of RBM47 significantly aggravated neointimal hyperplasia. In vitro, RBM47 promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, and EndMT. Mechanistically, RBM47 was predominantly localized in the nucleus, suggesting a role in alternative splicing. Transcriptome sequencing revealed that RBM47 promoted retention of exon 13 in SEC31A, thereby suppressing the generation of the SEC31A-Δ13 splice variant. This splice variant inhibited SMAD3 phosphorylation and its downstream signaling cascade. Conclusions: RBM47 promotes neointimal hyperplasia in autogenous AVF by inducing EndMT. Specifically, RBM47 regulates alternative splicing of SEC31A and reduces the production of the SEC31A-Δ13 splice variant, which inhibits SMAD3 phosphorylation. These findings reveal a novel mechanism by which RNA-binding proteins contribute to AVF stenosis and suggest RBM47 as a potential therapeutic target for preventing AVF failure. (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: All procedures involving human participants and human samples were conducted in accordance with the Declaration of Helsinki and were approved by the Institutional Review Board/Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (approval number: YJSKY2025-289). Written informed consent was obtained from all patients prior to surgery. All animal experiments were conducted in accordance with institutional guidelines for the care and use of laboratory animals and were approved by the Animal Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (approval number: YJSDW2025-167). Consent for publication: All authors agree to this submission. Competing interests: The authors declare no competing interests. |
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| Grant Information: | No. 82500915 The National Natural Science Foundation of China; No. 82170756 The National Natural Science Foundation of China; No. 2023ZX06C06 Key Research and Development of Heilongjiang Province; No. JD24D006 Science and Technology Innovation Base Award Program of Heilongjiang Province |
| Contributed Indexing: | Keywords: Alternative splicing; Arteriovenous fistula; EndMT; Neointimal hyperplasia; RNA-binding motif protein 47 |
| Substance Nomenclature: | 0 (RNA-Binding Proteins) |
| Entry Date(s): | Date Created: 20260710 Date Completed: 20261006 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| PubMed Central ID: | PMC13640188 |
| DOI: | 10.1186/s12882-026-05194-4 |
| PMID: | 42432548 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1471-2369 |
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| DOI: | 10.1186/s12882-026-05194-4 |