Metabolic dynamics of human external urethral sphincter myoblast differentiation and the effects of tricarboxylic acid cycle inhibition.

ABSTRACT: Stress urinary incontinence commonly arises with aging or following prostatectomy, yet its underlying mechanisms remain unclear. To address this, we investigated the role of metabolic pathways-particularly the tricarboxylic acid (TCA) cycle-in the differentiation of human external urethral sphincter myoblasts. Immortalized sphincter cells (US2-KD) were induced to differentiate over 192 h. Metabolomic profiling using gas chromatography-mass spectrometry, along with pathway enrichment analysis, identified key metabolic changes. Inhibition of mitochondrial pyruvate transport with UK5099 markedly suppressed TCA cycle metabolites, including citrate, α-ketoglutarate, fumarate, and malate. This inhibition also significantly reduced MYH7 expression and intracellular adenosine triphosphate levels t

SUBMITTER: Kai H 

PROVIDER: S-EPMC12331984 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature