TRIM24 Impediment suppresses VSMC modulation and attenuates neointimal hyperplasia via redox and autophagy pathways.
M, S., A, S., ZB, Z., Y, M., SV, P., K, C., & M, J. (2026). TRIM24 Impediment suppresses VSMC modulation and attenuates neointimal hyperplasia via redox and autophagy pathways.. Molecular biology reports. https://doi.org/10.1007/s11033-026-12470-x
M S, A S, ZB Z, Y M, SV P, K C, et al. TRIM24 Impediment suppresses VSMC modulation and attenuates neointimal hyperplasia via redox and autophagy pathways.. Molecular biology reports. 2026; doi: 10.1007/s11033-026-12470-x
M S, A S, ZB Z, et al. TRIM24 Impediment suppresses VSMC modulation and attenuates neointimal hyperplasia via redox and autophagy pathways.[J]. Molecular biology reports. 2026. DOI: 10.1007/s11033-026-12470-x.
@article{m2026,
author = {Singh M and Sarkar A and Zargar ZB and Mukheja Y and Pawar SV and Chopra K and Jain M},
title = {TRIM24 Impediment suppresses VSMC modulation and attenuates neointimal hyperplasia via redox and autophagy pathways.},
journal = {Molecular biology reports},
year = {2026},
doi = {10.1007/s11033-026-12470-x},
note = {PMID: 42525139},
}
TY - JOUR AU - Singh M AU - Sarkar A AU - Zargar ZB AU - Mukheja Y AU - Pawar SV AU - Chopra K AU - Jain M TI - TRIM24 Impediment suppresses VSMC modulation and attenuates neointimal hyperplasia via redox and autophagy pathways. T2 - Molecular biology reports PY - 2026 DO - 10.1007/s11033-026-12470-x AN - PMID:42525139 ER -
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.