Transcriptomic analysis identifies key genes and mechanisms involved in dibutyl phthalate-induced alteration in hepatic stellate cells

초록

Dibutyl phthalate (DBP) is a widely used phthalate plasticizer and endocrine disruptor implicated in hepatic injury and fibrosis. However, its direct impact on hepatic stellate cells (HSCs) remains insufficiently characterized. In this study, we examined DBP-induced transcriptomic alterations and functional pathways in HSCs. RNA sequencing of 42,844 genes identified 981 significantly differentially expressed genes (FDR < 0.05), followed by validation using qPCR and Western blot analysis. Gene Ontology (GO) and KEGG enrichment analyses revealed strong activation of endoplasmic reticulum (ER) stress, autophagy, apoptosis, and calcium signaling pathways. Heatmap clustering further highlighted upregulation of ER stress-and autophagy-related genes, consistent with increased autophagic degradation and apoptotic signaling. Notably, genes regulating Ca(2+)homeostasis were markedly dysregulated, showing enhanced expression of Ca2+-permeable channels and suppression of K(+)channels, indicating a shift in intracellular ion dynamics. Collectively, DBP exposure severely disrupts HSC transcriptomic equilibrium through concerted activation of ER stress, autophagy, apoptosis, and calcium signaling. These findings identify ER stress-Ca(2+)signaling crosstalk as a mechanistic hub linking DBP exposure to fibrogenic liver injury and establish a transcriptome-resolved framework for elucidating phthalate-induced hepatotoxicity and advancing risk assessment strategies.

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