2. Academic Validation
  3. Pantothenic acid ameliorates hepatic fibrosis by targeting IGFBP6 to regulate the TGF-β/SMADs pathway

Pantothenic acid ameliorates hepatic fibrosis by targeting IGFBP6 to regulate the TGF-β/SMADs pathway

  • Commun Biol. 2025 Jul 29;8(1):1127. doi: 10.1038/s42003-025-08527-5.
Zhengxin Jin 1,  Zhengsen Jin 2,  Zeyu Liu 3,  Yongcheng Yin 3,  Yuchen Zhang 3,  Ying Zhang 3,  Jianning Kang 1,  Yuepeng Fang 1,  Wei Jiang 3,  Bin Ning 4 5
Affiliations

Affiliations

  • 1 Jinan Central Hospital, Shandong University, No.105, Jiefang Road, Jinan, Shandong, China.
  • 2 Department of Clinical Pharmacology of Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
  • 3 Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
  • 4 Jinan Central Hospital, Shandong University, No.105, Jiefang Road, Jinan, Shandong, China. ningbin@sdu.edu.cn.
  • 5 Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China. ningbin@sdu.edu.cn.
PMID: 40730679 DOI: 10.1038/s42003-025-08527-5
Abstract

Hepatic fibrosis progression involves complex multicellular crosstalk, highlighting the critical need to identify key therapeutic targets. In this study, we identify insulin-like growth factor binding protein 6 (IGFBP6) as a marker specifically enriched in hepatic stellate cells (HSCs) and upregulated in viral hepatitis-associated fibrosis. Using thioacetamide (TAA)-induced mouse models and transforming growth factor-β (TGF-β)-stimulated cell models, we demonstrate the pro-fibrotic role of IGFBP6. Through network pharmacology screening, pantothenic acid (PA) is identified as a potent compound targeting IGFBP6. PA administration significantly reduces Collagen deposition, attenuates HSCs' activation, and decreases hepatic fibrosis-related markers. Notably, PA maintains efficacy in mouse models with established fibrosis. Mechanistically, PA directly interacts with IGFBP6, inducing ubiquitin-dependent degradation and inhibiting TGF-β/SMADs signaling. This study identifies IGFBP6 as a driver of hepatic fibrosis and validates PA as a potent therapeutic agent. Therefore, targeting IGFBP6 with PA offers a potential clinical treatment strategy for hepatic fibrosis.

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