Genome-wide Mendelian randomization mapping the influence of plasma proteome on major depressive disorder

Journal of Affective Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Repression of oxidative phosphorylation by NR2F2, MTERF3 and GDF15 in human skin under high-glucose stress

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103613 - 103613

Published: March 1, 2025

Lifestyle factors such as a Western diet or metabolic diseases like diabetes disrupt glucose homeostasis and induce stress responses, yet their impact on skin metabolism structural integrity remains poorly understood. Here, we performed multiomic bioenergetic analyses of human dermal fibroblasts (HDFs), equivalent dermis (HED), reconstructed (HRS), explants from diabetic patients. We found that 12 mM represses oxidative phosphorylation (OXPHOS) through dual mechanism: the glucose-dependent nuclear receptor NR2F2 activates mitochondrial transcription termination factor 3 (MTERF3) while inhibiting growth-differentiation 15 (GDF15). Promoter assays revealed MTERF3 is regulated by MYCN, whereas GDF15 modulated FOS. Consequently, OXPHOS proteins respiration were suppressed, overexpression additionally interfered with collagen biosynthesis. In contrast, supplementation fully rescued hyperglycemia-induced metabolomic alterations, suggesting pharmacological strategy to mitigate hyperglycemic damage in skin. Finally, silencing TFAM impaired fibroblast haptotaxis reconstruction, underscoring crucial role energetics structure function. Collectively, these findings identify NR2F2-MTERF3-GDF15 axis key mediator suppression highlight potential therapeutic target preserve under stress.

Language: Английский

Identifying Immune Response Protein Biomarkers in Parkinson’s-Related Cognitive Impairment and Depression

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Language: Английский