Journalartikel

Cathepsin L and B as Potential Markers for Liver Fibrosis: Insights From Patients and Experimental Models


AutorenlisteManchanda, Mansi; Das, Prasenjit; Gahlot, Gaurav P. S.; Singh, Ratnakar; Roeb, Elke; Roderfeld, Martin; Gupta, Siddhartha Datta; Saraya, Anoop; Pandey, R. M.; Chauhan, Shyam S.

Jahr der Veröffentlichung2017

ZeitschriftClinical and Translational Gastroenterology

Bandnummer8

ISSN2155-384X

Open Access StatusGold

DOI Linkhttps://doi.org/10.1038/ctg.2017.25

VerlagLippincott, Williams & Wilkins


Abstract

OBJECTIVES: Cathepsin L (CTSL) and B (CTSB) have a crucial role in extracellular matrix (ECM) degradation and tissue remodeling, which is a prominent feature of fibrogenesis. The aim of this study was to determine the role and clinical significance of these cathepsins in liver fibrosis.

METHODS: Hepatic histological CTSL and CTSB expression were assessed in experimental models of liver fibrosis, patients with liver cirrhosis, chronic viral hepatitis, and controls by real-time PCR and immunohistochemistry. Plasma levels of CTSL and CTSB were analyzed in 51 liver cirrhosis patients (Child-Pugh stages A, B and C) and 15 controls.

RESULTS: Significantly enhanced CTSL mRNA (P = 0.02) and protein (P = 0.01) levels were observed in the liver of carbon tetrachloride-treated mice compared with controls. Similarly, hepatic CTSL and CTSB mRNA levels (P = 0.02) were markedly wincreased in Abcb4(-/-) (ATP-binding cassette transporter knockout) mice compared with wild-type littermates. Elevated levels of CTSL and CTSB were also found in the liver (P = 0.001) and plasma (P < 0.0001) of patients with hepatic cirrhosis compared with healthy controls. Furthermore, CTSL and CTSB levels correlated well with the hepatic collagen (r = 0.5, P = 0.007; r = 0.64, P = 0.0001). CTSL and CTSB levels increased with the Child-Pugh stage of liver cirrhosis and correlated with total bilirubin content (r = 0.4/0.2; P <= 0.05). CTSL, CTSB, and their combination had a high diagnostic accuracy (area under the curve: 0.91, 0.89 and 0.96, respectively) for distinguishing patients from controls.

CONCLUSIONS: Our data demonstrate the overexpression of CTSL and CTSB in patients and experimental mouse models, suggesting their potential as diagnostic biomarkers for chronic liver diseases.




Zitierstile

Harvard-ZitierstilManchanda, M., Das, P., Gahlot, G., Singh, R., Roeb, E., Roderfeld, M., et al. (2017) Cathepsin L and B as Potential Markers for Liver Fibrosis: Insights From Patients and Experimental Models, Clinical and Translational Gastroenterology, 8, Article e99. https://doi.org/10.1038/ctg.2017.25

APA-ZitierstilManchanda, M., Das, P., Gahlot, G., Singh, R., Roeb, E., Roderfeld, M., Gupta, S., Saraya, A., Pandey, R., & Chauhan, S. (2017). Cathepsin L and B as Potential Markers for Liver Fibrosis: Insights From Patients and Experimental Models. Clinical and Translational Gastroenterology. 8, Article e99. https://doi.org/10.1038/ctg.2017.25



Schlagwörter


ACIDSCHRONIC HEPATITISCYSTEINE CATHEPSINSHEPATOCYTE APOPTOSISRENAL FIBROSIS


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