Growth Differentiation Factor 15 Inhibits Cardiac Fibrosis, Oxidative Stress, Inflammation, and Apoptosis in a Rat Model of Heart Failure with Preserved Ejection Fraction

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(2)

Published: Feb. 18, 2025

Background: Heart failure with preserved ejection fraction (HFpEF) is a systemic syndrome primarily associated fibrosis, oxidative stress, inflammation, and cellular apoptosis. Growth differentiation factor 15 (GDF15), biomarker commonly used in clinical studies, exhibits protective effects on the myocardium. Therefore, focus of present study to determine mechanism by which GDF15 protects cardiac function HFpEF. Methods: We conducted functional enrichment analysis protein-protein interaction network genes highly expressed HFpEF but lowly normal samples. established an rat model feeding rats high-fat diet administering N-omega-nitro-l-arginine-methyl ester (L-NAME) their drinking water silenced tail vein injection lentivirus (L3110). After 12 weeks feeding, echocardiographic examinations were performed. Following euthanasia rats, blood heart tissue samples collected. sections stained using Masson’s trichrome terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining methods. Western blot (WB) was employed concentrations relevant proteins. Results: The results showed that compared + MOCK group, HFpEF+silencing (siGDF15) group exhibited more severe dysfunction, significant decreases (p < 0.05) E/A ratio 0.001). WB demonstrated that, HFpEF+siGDF15 increased expression fibrosis-associated proteins, including collagen I 0.01), III α-smooth muscle actin (α-SMA) 0.01). Additionally, stress-associated biomarkers such as myeloperoxidase (MPO) 0.01) oxidized low-density lipoprotein (ox-LDL) inflammation-associated biomarkers, interleukin-1 beta (IL-1β) interleukin-6 (IL-6) interleukin-8 (IL-8) tumor necrosis α (TNFα) apoptosis-associated like cleaved caspase-3 BCL2-associated X (BAX) also upregulated group. Conclusions: Our research indicates preserves inhibiting myocardial reducing cell alleviating suppressing

Language: Английский

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JAK/STAT signaling as a key regulator of ferroptosis: mechanisms and therapeutic potentials in cancer and diseases

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 7, 2025

Ferroptosis is a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation, playing critical role in various diseases, including cancer, neurodegeneration, and tissue damage. This study reviews the intricate relationship between ferroptosis Janus kinase/signal transducer activator transcription (JAK/STAT) signaling pathway, highlighting its regulatory functions across multiple biological processes. Dysregulation JAK/STAT pathway implicated promoting or inhibiting ferroptosis, depending on context. JAK2 promotes activating STAT proteins, modulating expression key regulators like SLC7A11 GPX4, influencing iron homeostasis through pathways such as ferritinophagy hepcidin regulation. STAT1 activation primarily enhances suppression cystine-glutamate antiporter (System Xc-), leading to glutathione depletion contributing conditions Sjogren's syndrome age-related macular degeneration. In contrast, STAT3 plays protective upregulating which inhibits survival, particularly cancers hepatocellular carcinoma, prostate renal carcinoma. also discusses STAT6's involvement diseases asthma lung injury regulating antioxidant defenses. Furthermore, review explores potential therapeutic strategies targeting manipulate for disease treatment. cancer therapy, this can enhance effectiveness inducers, offering promising avenues overcome drug resistance. Additionally, interplay immune responses, oxidative stress, metabolism underscores significance progression intervention. By exploring these mechanisms, provides insights into development novel treatments modulation, with implications inflammatory neurodegenerative conditions.

Language: Английский

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Pinoresinol Diglucoside Attenuates Nuclear Receptor Coactivator 4‐Mediated Ferritinophagy Associated with Cisplatin‐Induced Hearing Loss

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Cisplatin can cause irreversible hearing loss. However, effective approaches to its prevention are not established. In this study, the effect of traditional Chinese medicine monomer pinoresinol diglucoside (PDG) is evaluated on cisplatin-induced ototoxicity and underlying mechanism action. PDG significantly increases cell viability inhibits reactive oxygen species production ferroptosis in cisplatin-treated House Ear Institute-Organ Corti 1 cells basilar membranes. partially restores loss caused by cisplatin. Transcriptome sequencing identifies Suppressor Cytokine Signaling (SOCS1), which elevated cisplatin-only group but reduced after application. SOCS1 a ferroptosis-promoting factor, knocking it down nuclear receptor coactivator 4 (NCOA4) ferritinophagy. Transmission electron microscopy reveals that reduces number autophagic lysosomes induced Co-immunoprecipitation performed confirm interaction between NCOA4. Taken together, these results indicate NCOA4-mediated ferritinophagy downregulating SOCS1, ototoxicity. This study provides new clinical option for

Language: Английский

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Natural products and ferroptosis: A novel approach for heart failure management

Phytomedicine, Journal Year: 2025, Volume and Issue: 142, P. 156783 - 156783

Published: April 18, 2025

Language: Английский

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Ferroptosis targeting offers a Therapeutic Target for Septic cardiomyopathy

Tissue and Cell, Journal Year: 2025, Volume and Issue: 95, P. 102930 - 102930

Published: April 25, 2025

Language: Английский

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Ginkgetin enhances breast cancer radiotherapy sensitization by suppressing NRF2-HO-1 axis activity

Toxicology and Applied Pharmacology, Journal Year: 2024, Volume and Issue: 495, P. 117199 - 117199

Published: Dec. 8, 2024

Language: Английский

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