2-B-YIA5-1 〇三原 大輝¹、水流 巧春²、黒澤 珠希¹、野々下 由真¹、山川 優輝¹、堀 正敏¹ Mihara Taiki¹, Yoshiharu Tsuru², Tamaki Kurosawa¹, Yuma Nonoshita¹, Yuki Yamakawa¹, Masatoshi Hori^{1 1}東京大・院農学生命科学・獣医学専攻　獣医薬理学研究室、²プライムテック株式会社・研究支援部 ¹Laboratory of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, ²Research Support Dev., PRIMETECH Corp. Background & Aims
Liver fibrosis could lead to fatal secondary diseases such as cirrhosis and hepatocellular carcinoma, including osteoporosis. However, there are no effective treatments for liver fibrosis and subsequent osteoporosis, necessitating new therapeutic targets. Recently, fibroblast growth factor 23 (FGF23) has garnered attention as a potential fibrosis-promoting factor. FGF23 also controls the phosphorus level in the body; excess FGF23 level causes phosphorus deficiency, resulting in impaired bone microstructure. In this study, we hypothesized that the FGF23 level increases with liver injury, which in turn induces liver fibrosis and osteoporosis.
Results
We found that carbon tetrachloride-induced liver injury increased the serum FGF23 level. RNA sequencing analysis using FGF23-treated hepatic stellate cells showed that FGF23 promotes the production of Matrisomes, which helps form the extracellular matrix. The FGF receptor antagonist pemigatinib alleviated carbon tetrachloride-induced liver fibrosis and dysfunction. Moreover, pemigatinib suppressed the deleterious alterations in bone density and microstructure.
Conclusion
We found that the serum FGF23 level increased with liver injury, FGF23 promoted liver fibrosis, and inhibition of FGF23–FGFR signaling alleviated liver fibrosis and subsequent osteoporosis. These findings suggest that FGF23–FGFR signaling may be a new therapeutic target for liver fibrosis and subsequent osteoporosis.