Transcription factors in liver fibrosis: Mechanistic insights and nanotechnology‑driven therapeutic strategies (Review)
Year: 2026
Type: review
Abstract: Liver fibrosis, a common pathological outcome of chronic liver diseases, is a dynamic process characterized by molecular and cell interactions. Transcription factors (TFs) are key in modulating gene expression programs that govern hepatocyte fate, metabolic homeostasis, inflammation and extracellular matrix remodeling. In hepatocytes, TFs such as hepatocyte nuclear factor 4α and FOXA2 serve a key role in maintaining metabolic balance, with their dysfunction leading to lipid accumulation, oxidative stress and profibrotic signaling. In non‑parenchymal cells, including hepatic stellate, Kupffer and liver sinusoidal and biliary epithelial cells, TFs such as YAP/TAZ, NF‑κB, STAT3 and GATA‑binding factor 4 regulate activation, proliferation and intercellular communication, thereby influencing fibrosis progression or resolution. Advances in single‑cell omics, spatial transcriptomics and epigenomics are elucidating the dynamic, cell type‑specific TF networks involved in fibrosis and identifying therapeutic targets. Nanotechnology presents strategies for precise modulation of TFs and selective targeting of hepatic cell populations, facilitated by nanocarriers that enable the delivery of nucleic acids, pathway inhibitors and epigenetic modulators. Preclinical studies indicate promising antifibrotic effects of nanodelivery systems, however, challenges related to biocompatibility, targeting efficiency and clinical translation persist. This review aimed to summarize TF‑mediated regulation in liver fibrosis and nanotechnology‑based therapeutic approaches as well as future directions for precision antifibrotic therapy.
Authors: Xianfei Zhou, Chongjun Yang, Zhiyong Weng, Lihua Li
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7223090366