ArticleDrug design, development and therapy2024
Trimetazidine Alleviates Bleomycin-Induced Pulmonary Fibrosis by Targeting the Long Noncoding RNA CBR3-AS1-Mediated miRNA-29 and Resistin-Like Molecule alpha 1: Deciphering a Novel Trifecta Role of LncRNA CBR3-AS1/miRNA-29/FIZZ1 Axis in Lung Fibrosis.
Article in Drug design, development and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Resistin in Tissue Remodeling and Fibrosis: A New Frontier.Biomolecules · 2026Review
- Combined Serum Expression of lncRNA CBR3-AS1 and miR-3163: Prognostic Significance and Underlying Mechanism in Severe Pneumonia.The clinical respiratory journal · 2026Article
- Construction of a Lysine Lactylation- and DNA Damage Repair-Related Gene Signature to Predict the Prognosis and Drug Sensitivity of Breast Cancer Patients.International journal of molecular sciences · 2026Article
- Cannabigerol (CBG) Modulates Neutrophil Activity and Ameliorates Rheumatoid Arthritis Pathogenesis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Rebamipide Reprograms Hepatic Networks to Prevent and Reverse Metabolic-Dysfunction-Associated Steatotic Liver Disease: Multi-Omics Insights and Histological Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Article
- Dendrobine's mechanism: alleviating cholesterol metabolism disorders via FXR/LXR modulation in NAFLD mouse livers.Frontiers in pharmacology · 2026Article
- Integrative Metabolomic, Network Pharmacology, and Experimental Evidence forPharmaceuticals (Basel, Switzerland) · 2025Article
- Fibrotic Disease of the Skin and Lung: Shared Pathways, Environmental Drivers, and Therapeutic Opportunities in a Changing Climate.International journal of molecular sciences · 2025Review
- Exploration of the anticancer efficacy of a novel 1,3-thiazole analog in an ehrlich ascites carcinoma model:RSC advances · 2025Article
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14 authors.
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Abstract
Introduction: Pulmonary fibrosis (PF) and tissue remodeling can greatly impair pulmonary function and often lead to fatal outcomes. Methodology: In the present study, we explored a novel molecular interplay of long noncoding (Lnc) RNA CBR3-AS1/ miRNA-29/ FIZZ1 axis in moderating the inflammatory processes, immunological responses, and oxidative stress pathways in bleomycin (BLM)-induced lung fibrosis. Furthermore, we investigated the pharmacological potential of Trimetazidine (TMZ) in ameliorating lung fibrosis. Results: Our results revealed that the BLM-treated group exhibited a significant upregulation in the expression of epigenetic regulators, lncRNA CBR3-AS1 and FIZZ1, compared to the control group (P<0.0001), along with the downregulation of miRNA-29 expression. Furthermore, Correlation analysis showed a significant positive association between lnc CBR3-AS1 and FIZZ1 (R=0.7723, p<0.05) and a significant negative association between miRNA-29 and FIZZ1 (R=-0.7535, p<0.05), suggesting lnc CBR3-AS1 as an epigenetic regulator of FIZZ1 in lung fibrosis. BLM treatment significantly increased the expression of Notch, Jagged1, Smad3, TGFB1, and hydroxyproline. Interestingly, the administration of TMZ demonstrated the ability to attenuate the deterioration effects caused by BLM treatment, as indicated by biochemical and histological analyses. Our investigations revealed that the therapeutic potential of TMZ as an antifibrotic drug could be ascribed to its ability to directly target the epigenetic regulators lncRNA CBR3-AS1/ miRNA-29/ FIZZ1, which in turn resulted in the mitigation of lung fibrosis. Histological and immunohistochemical analyses further validated the potential antifibrotic effects of TMZ by mitigating the structural damage associated with fibrosis. Discussion: Taken together, our study showed for the first time the interplay between epigenetic lncRNAs CBR3-AS1 and miRNA-29 in lung fibrosis and demonstrated that FIZZ1 could be a downregulatory gene for lncRNA CBR3-AS1 and miRNA-29. Our key findings demonstrate that TMZ significantly reduces the expression of fibrotic, oxidative stress, immunomodulatory, and inflammatory markers, along with epigenetic regulators associated with lung fibrosis. This validates its potential as an effective antifibrotic agent by targeting the CBR3-AS1/miRNA-29/FIZZ1 axis.
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