Decreased serum cathepsin S levels in patients with systemic sclerosis‐associated interstitial lung disease
- 8 June 2020
- journal article
- research article
- Published by Wiley in The Journal of Dermatology
- Vol. 47 (9), 1027-1032
- https://doi.org/10.1111/1346-8138.15458
Abstract
Cathepsin S (CTSS) is a lysosomal proteolytic enzyme regulating intracellular and extracellular biological activities, including immunity/inflammation and remodeling of vasculature and extracellular matrix, which are the three cardinal pathological events associated with systemic sclerosis (SSc). To elucidate the potential role of CTSS in the development of SSc, we investigated the clinical correlation of serum CTSS levels. Because serum CTSS levels were inversely correlated with estimated glomerular filtration rate (eGFR) in SSc patients with renal dysfunction (eGFR, 2), SSc patients with normal renal function (eGFR, ≥60 min/mL per 1.73 m2) were analyzed. Serum CTSS levels were significantly decreased in diffuse cutaneous SSc patients compared with limited cutaneous SSc patients and healthy controls. Among vascular and fibrotic clinical manifestations, Raynaud’s phenomenon and interstitial lung disease (ILD) were relevant to a significant decrease in serum CTSS levels. Importantly, serum CTSS levels negatively correlated with serum levels of Krebs von den Lungen‐6 and surfactant protein D in total SSc patients, while not correlating with modified Rodnan total skin thickness score and the percentage of predicted diffusion lung capacity for carbon monoxide and showing a positive trend with the percentage of predicted vital capacity. These results suggest a potential contribution of decreased CTSS expression to the development of ILD in patients with SSc.Keywords
Funding Information
- The Ministry of Health, Labour, and Welfare of Japan
This publication has 36 references indexed in Scilit:
- Cathepsin S Deficiency Results in Abnormal Accumulation of Autophagosomes in Macrophages and Enhances Ang II–Induced Cardiac InflammationPLOS ONE, 2012
- A Possible Contribution of Altered Cathepsin B Expression to the Development of Skin Sclerosis and Vasculopathy in Systemic SclerosisPLOS ONE, 2012
- Specialized roles for cysteine cathepsins in health and diseaseJCI Insight, 2010
- The impact of Fli1 deficiency on the pathogenesis of systemic sclerosisJournal of Dermatological Science, 2010
- Exhaled nitric oxide, but not serum nitrite and nitrate, is a marker of interstitial lung disease in systemic sclerosisNitric Oxide, 2009
- Systemic sclerosis fibroblasts inhibitin vitro angiogenesis by MMP-12-dependent cleavage of the endothelial cell urokinase receptorThe Journal of Pathology, 2006
- Cathepsin S Controls Angiogenesis and Tumor Growth via Matrix-derived Angiogenic FactorsJournal of Biological Chemistry, 2006
- The effect of bosentan on matrix metalloproteinase-9 levels in patients with systemic sclerosis-induced pulmonary hypertensionCurrent Medical Research and Opinion, 2005
- Deficiency of the Cysteine Protease Cathepsin S Impairs Microvessel GrowthCirculation Research, 2003
- Cysteine Proteases and Their InhibitorsChemical Reviews, 1997