Pharmacological reports : PR · 2026
Trimetazidine modulates angiogenesis, inflammation, and metabolism-related gene expression to promote diabetic foot ulcer healing: a transcriptomic analysis.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Dulcic Dorian, Dumancic Lucija, Gregorek Andrea Crkvenac, Kirhmajer Majda Vrkic, Likic Robert
Аннотация
BACKGROUND: Diabetic foot ulcers (DFUs) are a chronic complication of diabetes associated with impaired healing and tissue ischemia.
AIM: This study explores the transcriptional effects of trimetazidine (TMZ) in wound-relevant human cell models to generate hypotheses regarding its potential mechanisms of action.
METHODS: We conducted a secondary analysis of LINCS Phase 5 transcriptomic data to evaluate TMZ-induced gene expression in four human cell lines relevant to DFU pathophysiology: HUVEC (endothelial), THP1 (monocytic), A375 (keratinocytic-like), and MCF7 (epithelial-like).
RESULTS: TMZ induced 700-900 differentially expressed genes per cell line, with distinct yet convergent responses across models. A consistent activation of the PI3K-Akt signaling pathway was observed, along with modulation of noncanonical NF-κB components such as RELB and CXCL2. TMZ promoted metabolic reprogramming, including SIRT3 upregulation and glycolysis inhibition, and selectively regulated extracellular matrix remodeling genes. Importantly, pro-angiogenic and anti-inflammatory signatures emerged independently of VEGF, with notable downregulation of PTGS2 and TLR4.
CONCLUSION: These results highlight TMZ's potential to modulate gene networks associated with angiogenesis, inflammation, and metabolism. The findings are exploratory and warrant validation in preclinical models to assess their therapeutic relevance.
AIM: This study explores the transcriptional effects of trimetazidine (TMZ) in wound-relevant human cell models to generate hypotheses regarding its potential mechanisms of action.
METHODS: We conducted a secondary analysis of LINCS Phase 5 transcriptomic data to evaluate TMZ-induced gene expression in four human cell lines relevant to DFU pathophysiology: HUVEC (endothelial), THP1 (monocytic), A375 (keratinocytic-like), and MCF7 (epithelial-like).
RESULTS: TMZ induced 700-900 differentially expressed genes per cell line, with distinct yet convergent responses across models. A consistent activation of the PI3K-Akt signaling pathway was observed, along with modulation of noncanonical NF-κB components such as RELB and CXCL2. TMZ promoted metabolic reprogramming, including SIRT3 upregulation and glycolysis inhibition, and selectively regulated extracellular matrix remodeling genes. Importantly, pro-angiogenic and anti-inflammatory signatures emerged independently of VEGF, with notable downregulation of PTGS2 and TLR4.
CONCLUSION: These results highlight TMZ's potential to modulate gene networks associated with angiogenesis, inflammation, and metabolism. The findings are exploratory and warrant validation in preclinical models to assess their therapeutic relevance.