ArticleThe Journal of biological chemistry2012
Cathepsin B overexpression due to acid sphingomyelinase ablation promotes liver fibrosis in Niemann-Pick disease.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Retention of lysosomal acid sphingomyelinase protects from Niemann-Pick Disease.Neurobiology of disease · 2025Article
- Cathepsin D is essential for the degradomic shift of macrophages required to resolve liver fibrosis.Molecular metabolism · 2024Article
- The Effects of Cathepsin B Inhibition in the Face of Diffuse Traumatic Brain Injury and Secondary Intracranial Pressure Elevation.Biomedicines · 2024Article
- The impact of sphingomyelin on the pathophysiology and treatment response to olipudase alfa in acid sphingomyelinase deficiency.Genetics in medicine open · 2024Review
- Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis.International journal of molecular sciences · 2023Article
- Integrative transcriptomic and proteomic analysis reveals mechanisms of silica-induced pulmonary fibrosis in rats.BMC pulmonary medicine · 2022Article
- Article
- Acid Sphingomyelinase, a Lysosomal and Secretory Phospholipase C, Is Key for Cellular Phospholipid Catabolism.International journal of molecular sciences · 2021Review
- Sphingomyelinases and Liver Diseases.Biomolecules · 2020Review
- Cathepsin B deficiency ameliorates liver lipid deposition, inflammatory cell infiltration, and fibrosis after diet-induced nonalcoholic steatohepatitis.Translational research : the journal of laboratory and clinical medicine · 2020Article
- Can cysteinyl cathepsin activity control diet-induced NAFLD?International journal of cardiology. Heart & vasculature · 2020Article
- GNS561 acts as a potent anti-fibrotic and pro-fibrolytic agent in liver fibrosis through TGF-β1 inhibition.Therapeutic advances in chronic disease · 2020Article
- Portal hypertension: not a common Niemann.BMJ case reports · 2019Article
- Article
- Cathepsin S regulates renal fibrosis in mouse models of mild and severe hydronephrosis.Molecular medicine reports · 2019Article
- Combinatorial Omics Analysis Reveals Perturbed Lysosomal Homeostasis in Collagen VII-deficient Keratinocytes.Molecular & cellular proteomics : MCP · 2018Article
- Acid Sphingomyelinase Inhibition Prevents Development of Sepsis Sequelae in the Murine Liver.Scientific reports · 2017Article
- Cathepsin L and B as Potential Markers for Liver Fibrosis: Insights From Patients and Experimental Models.Clinical and translational gastroenterology · 2017Article
- Phagolysosome acidification is required for silica and engineered nanoparticle-induced lysosome membrane permeabilization and resultant NLRP3 inflammasome activity.Toxicology and applied pharmacology · 2017Article
- Lysosomal and Mitochondrial Liaisons in Niemann-Pick Disease.Frontiers in physiology · 2017Review
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Niemann-Pick disease (NPD) is a lysosomal storage disease caused by the loss of acid sphingomyelinase (ASMase) that features 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-null mice and their role in liver fibrosis. Surprisingly, HSCs from ASMase-knock-out mice exhibit increased basal level and activity of CtsB as well as its in vitro processing in culture, paralleling the enhanced expression of fibrogenic markers α-smooth muscle actin (α-SMA), TGF-β, and pro-collagen-α1(I) (Col1A1). Moreover, pharmacological inhibition of CtsB blunted the expression of α-SMA and Col1A1 and proliferation of HSCs from ASMase-knock-out mice. Consistent with the enhanced activation of CtsB in HSCs from ASMase-null mice, the in vivo liver fibrosis induced by chronic treatment with CCl(4) increased in ASMase-null compared with wild-type mice, an effect that was reduced upon CtsB inhibition. In addition to liver, the enhanced proteolytic processing of CtsB was also observed in brain and lung of ASMase-knock-out mice, suggesting that the overexpression of CtsB may underlie the phenotype of NPD. Thus, these findings reveal a functional relationship between ASMase and CtsB and that the ablation of ASMase leads to the enhanced processing and activation of CtsB. Therefore, targeting CtsB may be of relevance in the treatment of liver fibrosis in patients with NPD.
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