AUTHOR=Zhao Jinfeng , Xu Xiaodan , Gou Qingyun , Zheng Qipeng , Ge Liang , Chen Lingzhi , Zhang Cong , Ma Hui , Lin Shuxiang , Hu Xiaoli , Zhan Jianghua 

TITLE=TGF-β1-Mediated Leukocyte Cell-Derived Chemotaxin 2 Is Associated With Liver Fibrosis in Biliary Atresia

JOURNAL=Frontiers in Pediatrics

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.901888

DOI=10.3389/fped.2022.901888

ISSN=2296-2360

ABSTRACT=<sec><title>Objective</title><p>Biliary atresia (BA) presents as a severe infantile cholangiopathy disease, characterized by progressive liver fibrosis and the resulting poor prognosis. Leukocyte cell-derived chemotaxin 2 (LECT2) was proposed as the key gene associated with hepatic fibrosis in BA, but the molecular mechanism is unclear. This study aims to investigate the function of LECT2 in BA.</p></sec><sec><title>Methods</title><p>A total of 53 patients were enrolled in this study; 36 patients with BA, and 17 control patients with cholestasis, including congenital biliary dilations, biliary hypoplasia, and inspissated bile syndrome. The role of LECT2 in BA was analyzed using histological and cytological tests. The correlation between LECT2 and infiltrating immune cells was further analyzed by bioinformatics. The analyses were conducted using correlational analyses and ROC curves.</p></sec><sec><title>Results</title><p>LECT2 was highly expressed in infants with BA and positively related with fibrosis (0.1644 ± 0.0608 vs. 0.0779 ± 0.0053, <italic>p</italic> &lt; 0.0001; <italic>r</italic><sub><italic>s</italic></sub> = 0.85, <italic>p</italic> &lt; 0.0001). Serum levels of LECT2 showed high distinguishing features for patients with BA having an AUC of 0.95 (95% CI: 0.90–1.00). CD163 was highly expressed in the aggravation of fibrosis (0.158 ± 0.062 vs. 0.29 ± 0.078, <italic>p</italic> &lt; 0.0001), and the expression of LECT2 was positively correlated with the accumulation of CD163<sup>+</sup> macrophages (<italic>r</italic> = 0.48, <italic>p</italic> = 0.003). The bioinformatic analysis also showed that LECT2 was positively correlated with macrophage M2 (<italic>r</italic> = 0.34, <italic>p</italic> = 0.03). TGF-β1 and CD163 colocalized to the portal area in the livers of patients with BA. Moreover, TGF-β1 upregulated the expression of LECT2.</p></sec><sec><title>Conclusion</title><p>LECT2 is highly expressed in both BA liver tissue and serum, and serum LECT2 is a potential diagnostic biomarker of BA. Meanwhile, TGF-β1 is secreted by macrophages to regulate LECT2 associated with BA liver fibrosis.</p></sec>