ArticleThe Journal of biological chemistry2014
Regulation of TGF-β1-driven differentiation of human lung fibroblasts: emerging roles of cathepsin B and cystatin C.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 71 citations in OpenAlex.
- Analysis of the Clinical Effects of the Combination of Mycophenolate Mofetil with Either Tacrolimus or Cyclophosphamide.Clinics (Sao Paulo, Brazil) · 2020Trial
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Targeting Lp-PLA2 inhibits profibrotic monocyte-derived macrophages in silicosis through restoring cardiolipin-mediated mitophagy.Cellular & molecular immunology · 2025Article
- Diagnostic value of serum TGF-β1 and CysC in type 2 diabetic kidney disease: a cross-sectional study.Frontiers in medicine · 2025Article
- Development of a Novel Biomarker for the Progression of Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2024Article
- Elucidating the causal associations and mechanisms between circulating immune cells and idiopathic pulmonary fibrosis: new insights from Mendelian randomization and transcriptomics.Frontiers in immunology · 2024Article
- The Role of Cathepsin B in Pathophysiologies of Non-tumor and Tumor tissues: A Systematic Review.Journal of Cancer · 2023Review
- Cleavage of Occludin by Cigarette Smoke-Elicited Cathepsin S Increases Permeability of Lung Epithelial Cells.Antioxidants (Basel, Switzerland) · 2022Article
- Inflammatory serum factors from aortic valve stenosis patients modulate sex differences in valvular myofibroblast activation and osteoblast-like differentiation.Biomaterials science · 2022Article
- The physiological and pathophysiological roles of the autophagy lysosomal system in the conventional aqueous humor outflow pathway: More than cellular clean up.Progress in retinal and eye research · 2022Review
- Review
- Overview of positron emission tomography in functional imaging of the lungs for diffuse lung diseases.The British journal of radiology · 2022Review
- Lysosomal peptidases-intriguing roles in cancer progression and neurodegeneration.FEBS open bio · 2022Review
- Role of cystatin C in urogenital malignancy.Frontiers in endocrinology · 2022Review
- Cathepsin B Localizes in the Caveolae and Participates in the Proteolytic Cascade in Trabecular Meshwork Cells. Potential New Drug Target for the Treatment of Glaucoma.Journal of clinical medicine · 2020Article
- Pressure overload promotes cystatin C secretion of cardiomyocytes to regulate the MAPK signaling pathway and mediate cardiac hypertrophy.Annals of translational medicine · 2020Article
- 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
- Cysteinyl cathepsins in cardiovascular diseases.Biochimica et biophysica acta. Proteins and proteomics · 2020Review
- Vitamin D Attenuates Loss of Endothelial Biomarker Expression in Cardio-Endothelial Cells.International journal of molecular sciences · 2020Article
- Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung matrix homeostasis partly depends on the fine regulation of proteolytic activities. We examined the expression of human cysteine cathepsins (Cats) and their relative contribution to TGF-β1-induced fibroblast differentiation into myofibroblasts. Assays were conducted using both primary fibroblasts obtained from patients with idiopathic pulmonary fibrosis and human lung CCD-19Lu fibroblasts. Pharmacological inhibition and genetic silencing of Cat B diminished α-smooth muscle actin expression, delayed fibroblast differentiation, and led to an accumulation of intracellular 50-kDa TGF-β1. Moreover, the addition of Cat B generated a 25-kDa mature form of TGF-β1 in Cat B siRNA-pretreated lysates. Inhibition of Cat B decreased Smad 2/3 phosphorylation but had no effect on p38 MAPK and JNK phosphorylation, indicating that Cat B mostly disturbs TGF-β1-driven canonical Smad signaling pathway. Although mRNA expression of cystatin C was stable, its secretion, which was inhibited by brefeldin A, increased during TGF-β1-induced differentiation of idiopathic pulmonary fibrosis and CCD-19Lu fibroblasts. In addition, cystatin C participated in the control of extracellular Cats, because its gene silencing restored their proteolytic activities. These data support the notion that Cat B participates in lung myofibrogenesis as suggested for stellate cells during liver fibrosis. Moreover, we propose that TGF-β1 promotes fibrosis by driving the effective cystatin C-dependent inhibition of extracellular matrix-degrading Cats.
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