Multi-Layer Omics Analysis Identifies Anxa3 and Coro1a as Candidate Targets of Pien Tze Huang in a Mouse Model of Liver Fibrosis

作者：H Wu, Longhui Gao, Xianglong Zhao, Xiangyi Li, Y W Lin, Le Chen, Li Li, Lu Shen, Wei Bao, Jinhang Zhu, Cong Huai, Zhiliang Chen, Yichao Zhuang, Shengying Qin · 发表于：Biomedicines · 年份：2026 · DOI：10.3390/biomedicines14071550 · 研究领域：Liver physiology and pathology、Proteoglycans and glycosaminoglycans research、Liver Disease Diagnosis and Treatment

Background/Objectives: Liver fibrosis, a wound-healing response to chronic liver injury characterized by excessive extracellular matrix (ECM) accumulation, represents a major global health burden with no approved anti-fibrotic therapies. Pien Tze Huang (PZH), an officially approved traditional Chinese medicine (NMPA Drug Approval No. Z35020243), has demonstrated hepatoprotective effects, yet its epigenetic mechanisms in fibrosis treatment remain unexplored. Methods: We performed the first integrated methylome–transcriptome–proteome analysis to investigate PZH’s anti-fibrotic mechanisms in a CCl4-induced mouse model using reduced representation bisulfite sequencing (RRBS), RNA-seq, and TMT-labeled LC-MS/MS. Results: We identified 10,974 differentially methylated loci (DMLs) and 773 differentially expressed genes (DEGs) modulated by PZH treatment. Integration analysis revealed ANXA3 and CORO1A as candidate therapeutic targets exhibiting significant inverse methylation-expression correlations validated at both transcriptomic and proteomic levels. Notably, PZH treatment modulated the CRLF-CLCF1 cytokine complex and the EGR-3 transcription factor network (42/44 genes enriched), suggesting broad transcriptional reprogramming in fibrotic liver. Protein–protein interaction (PPI) analysis highlighted key gene pairs such as Dnmt1-Uhrf1, Cbfb-Runx1, and Col4a1-Col4a2, implicating PZH in epigenetic maintenance, transcription factor regulation, and ECM remodeling. Conclusions: These findi...