SULT2B1 promotes cholangiocyte epithelial-mesenchymal transition in biliary atresia: one baby step or a giant leap in the pathogenesis of biliary atresia?

Biliary atresia (BA) is a progressive fibro-inflammatory cholangiopathy and is the most common indication for paediatric liver transplantation. Its pathogenesis remains elusive, and Kasai portoenterostomy is still the mainstay of management, with no current disease-modifying medical treatments available. The study by Yang et al. aims to further elucidate the pathogenesis of BA by exploring mechanisms of epithelial-mesenchymal transition (EMT) in BA, finding evidence that SULT2B1 promotes EMT via the Wnt/β-catenin pathway and MMP7. SULT2B1 was found to be overexpressed in BA livers, and increased expression was associated with the severity of fibrosis and poor prognosis. There was evidence that SULT2B1 expression was correlated with MMP7-mediated epithelial-mesenchymal cholangiocyte transition. In vitro studies showed that TGF-β1 treatment led to overexpression of SULT2B1 and promoted the EMT process via the Wnt/β-catenin/MMP7 pathway, while silencing of SULT2B1 reduced this. These findings represent a step forward in our understanding of the pathogenesis of BA, but further work is needed to translate this to clinical practice. The work of Yang et al. suggests multiple possible routes for this, including further investigation of the potential for SULT2B1 blockade, use of MMP7 as a prognostic marker or as a therapeutic target, and investigation of the relationship between SULT2B1 and CMV.