Int Immunopharmacol. 2025 May 6;157:114744. doi: 10.1016/j.intimp.2025.114744. Online ahead of print.
ABSTRACT
BACKGROUND: Liver fibrosis is one of the main severe pathological consequences of obstructive jaundice, and an effective treatment strategy is urgently needed. Filamin-binding LIM protein 1 (FBLIM1) is associated with fibrosis, however, there is no evidence to show the effect of FBLIM1 on obstructive jaundice.
METHODS: In our study, we investigated the function of FBLIM1 in bile duct ligation (BDL) rat models and human hepatic stellate cell (HSC) line LX-2.
RESULTS: Our findings confirmed that FBLIM1 was highly expressed in liver tissues of BDL rats. Liver histopathological injury, liver fibrosis, and inflammation response in BDL rats were attenuated by FBLIM1 knockdown. Moreover, FBLIM1 knockdown blocked the TGF-β signaling pathway in BDL rats. The results in TGF-β1-stimulation LX-2 cells further confirmed that FBLIM1 promoted LX-2 cell activation and fibrosis by regulating the TGF-β signaling pathway. FBLIM1 was further demonstrated to be modulated by Wilms’s tumor 1-associating protein (WTAP), which was highly expressed in liver tissues of BDL rats. WTAP stabilized FBLIM1 mRNA and regulated FBLIM1 expression in an m6A-dependent manner.
CONCLUSION: Our findings provide evidence indicating that FBLIM1 promotes liver fibrosis via regulating the TGF-β signaling pathway through WTAP-mediated m6A modification. The WTAP/FBLIM1/TGF-β axis may be a potential therapeutic target against obstructive jaundice.
PMID:40334627 | DOI:10.1016/j.intimp.2025.114744
