Animal Cells and Systems · Available online 18 May 2026 · In press · DOI 10.1080/19768354.2026.2671489
Hee Young Chae, Ji Yeong Park, Hyejin Hyung, Jiwon Ko, Su-Geun Lim, Young Jin Lee, Myoung Ok Kim, Song Park, Dong Kyu Choi, Soyoung Jang, Zae Young Ryoo, Soyeon Jang
Hepatic inflammation plays a key role in acute and chronic liver diseases by driving hepatocellular injury and promoting disease progression. However, the molecular mechanisms that maintain hepatic immune homeostasis remain unclear. Cathepsin A (Ctsa), a lysosomal serine carboxypeptidase involved in protein degradation and enzyme stabilization, has been implicated in lysosomal storage disorders. However, its role in liver immunity is poorly understood. Given the emerging evidence that lysosomal proteases contribute to immune regulation and inflammatory signaling, Ctsa is a promising yet underexplored candidate for elucidating how lysosomal proteases influence hepatic inflammation. To address this gap, this study aimed to investigate Ctsa function using Ctsa knockout (Ctsa-/-) mice. Under basal conditions, Ctsa-/- mice exhibited splenic immune activation and relative hepatomegaly accompanied by histological alterations. Following lipopolysaccharide challenge, the mice developed aggravated liver injury with elevated aminotransferase levels, enhanced immune cell infiltration, and increased pro-inflammatory cytokine expression. These inflammatory changes were accompanied by increased hepatocellular apoptosis, as evidenced by elevated Bax/Bcl-2 ratio, cleaved caspase-3 expression, and increased TUNEL-positive cells. Collectively, these findings indicate that Ctsa contributes to the regulation of hepatic immune and cellular homeostasis, and its loss increases susceptibility to inflammatory liver injury.
Abstract from DOAJ. Public domain (CC0 1.0).
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Chae, H., Park, J., Hyung, H., et al. (2026). Cathepsin A deficiency exacerbates LPS-induced inflammatory liver injury and apoptosis. Animal Cells and Systems. https://doi.org/10.1080/19768354.2026.2671489