Our recent work published in the Journal of Biological Chemistry: “Cathepsin B overexpression due to Acid Sphingomyelinase ablation promotes liver fibrosis in Niemann-Pick disease” features the novel participation of cathepsins in Niemann-Pick disease (NPD), a lysosomal storage disease caused by the loss of acid sphingomyelinase (ASMase) characterized by neurodegeneration and liver disease.
Because ASMase-knock-out mice models NPD and our previous findings revealed that ASMase activates cathepsins B/D (CtsB/D), our aim was to investigate the expression and processing of CtsB/D in hepatic stellate cells (HSCs) from ASMase-KO mice and their role in liver fibrosis. Surprisingly, HSCs from ASMase-knock-out mice exhibit increased basal level and activity of CtsB. Consistent with the enhanced activation of CtsB in HSCs from ASMase-KO mice, the in vivo liver fibrosis induced by chronic treatment with CCl(4) increased in ASMase-KO compared with wild-type mice, and was reduced upon CtsB inhibition. In addition to liver, the enhanced CtsB was also observed in brain and lung of ASMase-KO mice, suggesting that the overexpression of CtsB may underlie the phenotype of NPD. Therefore, targeting CtsB may be of relevance in the treatment of liver fibrosis in patients with NPD.
For more information: Moles A/Tarrats N et al, J Biol Chem 287(2):1178-88,2012.