Academic Journal
TRIM24 Impediment suppresses VSMC modulation and attenuates neointimal hyperplasia via redox and autophagy pathways.
| Τίτλος: | TRIM24 Impediment suppresses VSMC modulation and attenuates neointimal hyperplasia via redox and autophagy pathways. |
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| Συγγραφείς: | Singh M; Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India., Sarkar A; Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India., Zargar ZB; Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India., Mukheja Y; Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India., Pawar SV; Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India., Chopra K; Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India., Jain M; Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, 160014, Chandigarh, India. jainm@pu.ac.in. |
| Πηγή: | Molecular biology reports [Mol Biol Rep] 2026 Jul 29; Vol. 53 (1). Date of Electronic Publication: 2026 Jul 29. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Dordrecht, Boston, Reidel. |
| Ιατρικοί όροι (MeSH): | Autophagy*/drug effects , Muscle, Smooth, Vascular*/metabolism , Muscle, Smooth, Vascular*/cytology , Muscle, Smooth, Vascular*/pathology , Neointima*/metabolism , Neointima*/pathology , Neointima*/genetics , Myocytes, Smooth Muscle*/metabolism , Myocytes, Smooth Muscle*/drug effects , Carrier Proteins*/metabolism , Carrier Proteins*/genetics , Carrier Proteins*/antagonists & inhibitors, Cell Proliferation/drug effects ; Hyperplasia/metabolism ; Cell Movement/drug effects ; Apoptosis/drug effects ; Signal Transduction/drug effects ; Becaplermin/pharmacology ; Animals ; Mice ; Oxidation-Reduction ; Humans ; Cells, Cultured ; Male ; Mice, Inbred C57BL |
| Περίληψη: | Background: Excessive vascular smooth muscle cell (VSMC) proliferation/survival is a critical event underlying restenosis and vascular remodeling. Tripartite motif-containing 24 (TRIM24) is an oncogenic TRIM family protein with E3 ubiquitin ligase and transcriptional co-regulator functions. This study aimed to elucidate the critical role of TRIM24 in modulating VSMC functions and neointimal hyperplasia. Methods and Results: Our in-silico network pharmacology analysis revealed that the TRIM24 inhibitor, IACS-9571, engages multiple hub genes and key pathways involved in VSMC proliferation, apoptosis, autophagy, migration, and extracellular matrix remodeling. Using Western blot and immunofluorescence analysis, we found that platelet-derived growth factor-BB (PDGF-BB) stimulation of murine primary aortic VSMCs, significantly upregulated TRIM24 expression. SiRNA-mediated knockdown of TRIM24 attenuated PDGF-BB-induced VSMC proliferation. Pharmacological inhibition of TRIM24 using IACS-9571 markedly suppressed PDGF-BB-induced VSMC proliferation, migration, and phenotypic switching. Furthermore, TRIM24 blockade enhanced autophagy in VSMCs, as evidenced by elevated LC3 and Beclin-1 protein levels, accumulation of LC3 puncta and transcriptional upregulation of autophagy-related genes, namely ATG7 and ATG4B. Also, TRIM24 inhibition reduced AKT and mTOR activation compared to PDGF-BB-stimulated VSMCs. Concurrently, TRIM24 inhibition elevated mitochondrial ROS levels, upregulated BAX expression, a pro-apoptotic gene, and significantly enhanced apoptosis, as confirmed by TUNEL and Annexin V/PI assays. In vivo, Immunofluorescence analysis demonstrated elevated TRIM24 expression within the neointimal regions. Perivascular application of the TRIM24 inhibitor prevented wire injury-induced neointimal hyperplasia. Conclusion: These findings identify TRIM24 as a key regulator of VSMC proliferation, migration, and phenotypic switching. Targeting TRIM24 promotes autophagy and induces apoptosis, offering a promising strategy to limit neointimal hyperplasia and pathological vascular remodeling. (© 2026. The Author(s), under exclusive licence to Springer Nature B.V.) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: The Institutional Animal Ethics Committee (IAEC) approved protocols that were followed in all animal experiments and conducted as per guidelines of the “Committee for Control and Supervision of Experiments on Animals” for use & care of experimental animals (Approval No. PU/45/99/CPCSEA/IAEC/2024/923). No human subjects have been used in the study. Competing interests: The authors declare no competing interests. |
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| Grant Information: | BT/RLF/Re-entry/28/2019 Ramalingaswami Re-entry fellowship; SUR/2022/002069 Department of Science & Technology |
| Contributed Indexing: | Keywords: Autophagy; Neointimal hyperplasia; Phenotypic switching; TRIM24; Vascular smooth muscle cells |
| Substance Nomenclature: | 0 (Carrier Proteins) 1B56C968OA (Becaplermin) 0 (TRIM24 protein, human) |
| Entry Date(s): | Date Created: 20260729 Date Completed: 20260729 Latest Revision: 20261010 |
| Update Code: | 20261010 |
| DOI: | 10.1007/s11033-026-12470-x |
| PMID: | 42525139 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1573-4978 |
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| DOI: | 10.1007/s11033-026-12470-x |