β -Klotho inhibited the epithelial-mesenchymal transition of liver sinusoidal endothelial cells to alleviate schistosomiasis liver fibrosis

Jiang, T; Li, Q; Yu, Z; Cui, X; Mo, X; Chen, Q; Chen, Y; Li, X; Wei, M; Guo, Z; Hu, Y; Li, S

Journal article

β -Klotho inhibited the epithelial-mesenchymal transition of liver sinusoidal endothelial cells to alleviate schistosomiasis liver fibrosis

Abstract:: Schistosomiasis is a neglected zoonotic disease, and the liver fibrosis induced by Schistosoma japonicum infection poses a significant threat to human health. Traditionally, liver fibrosis in schistosomiasis has been attributed to eggs deposited in the liver, which trigger hepatic inflammation and fibrosis. However, our study reveals that schistosomula migration to the liver induces epithelial-to-mesenchymal transition (EMT) in liver sinusoidal endothelial cell (LSEC), thereby contributing to the progression of liver fibrosis. In the early stage of S. japonicum infection, mice exhibited a reduction in the proportion of LSEC and impairment of their function. RNA-sequencing revealed significant alterations in β-Klotho (KLB) expression in injured LSEC. Although KLB is known to exert anti-inflammatory functions as a co-receptor for fibroblast growth factor (FGF) in the liver, its role in LSEC EMT and schistosomiasis-induced liver fibrosis was unclear. Using SK-Hep1 cells, we found that KLB knockdown exacerbated EMT, whereas KLB over-expression attenuated EMT and decreased TGFβ1 secretion from LSEC, thereby suppressing LX-2 activation. In mice infected with S. japonicum, treatment with recombinant KLB protein or AAV8-KLB increased the LSEC population, mitigated EMT in both LSEC and liver tissues, ameliorated hepatic fibrosis, and inhibited TGFβ1 pathway activation. Our study reveals that KLB suppresses LSEC EMT induced by liver-stage schistosomula and TGFβ1 secretion, thereby inhibiting HSC activation and reducing liver fibrosis. Our findings highlight KLB as a promising therapeutic target for hepatic fibrosis in schistosomiasis.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Jiang, T., Li, Q., Yu, Z., Cui, X., Mo, X., Chen, Q., Chen, Y., Li, X., Wei, M., Guo, Z., Hu, Y., & Li, S. (2026). β -Klotho inhibited the epithelial-mesenchymal transition of liver sinusoidal endothelial cells to alleviate schistosomiasis liver fibrosis. PLoS Pathogens, 22(5), e1014148.

MLA Style

Jiang, T, et al. “β -Klotho Inhibited the Epithelial-Mesenchymal Transition of Liver Sinusoidal Endothelial Cells to Alleviate Schistosomiasis Liver Fibrosis.” PLoS Pathogens, vol. 22, no. 5, 2026, p. e1014148.

Chicago Style

Jiang, T, Q Li, Z Yu, et al. 2026. “β -Klotho Inhibited the Epithelial-Mesenchymal Transition of Liver Sinusoidal Endothelial Cells to Alleviate Schistosomiasis Liver Fibrosis.” PLoS Pathogens 22 (5): e1014148.
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