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Journal Articles FASEB Journal Year : 2023

ADAMTS12 is a stromal modulator in chronic liver disease

Abstract

Adamalysins, a family of metalloproteinases containing disintegrin and (ADAMs) ADAM with thrombospondin motifs (ADAMTSs), belong to the matrisome play important roles in various biological pathological processes, such as development, immunity cancer. Using liver cancer dataset from International Cancer Genome Consortium, we developed an extensive silico screening that identified cluster adamalysins co-expressed livers patients hepatocellular carcinoma (HCC). Within this cluster, ADAMTS12 expression was highly associated recurrence risk poorly differentiated HCC signatures. We showed expressed stromal cells tumor adjacent fibrotic tissues patients, more specifically activated stellate cells. mouse model carbon tetrachloride-induced injury, Adamts12 strongly transiently after 24 h acute treatment, fibrosis exacerbated Adamts12-null mice submitted chronic injury. HSC-derived LX-2 cell line, silencing resulted profound changes gene program. In particular, genes previously reported be induced upon HSC activation, PAI-1, were mostly down-regulated following knock-down. The phenotype these changed less state, showing altered actin network decreased nuclear spreading. These phenotypic changes, together down-regulation offset by TGF-β treatment. present study thus identifies modulator differentiation, new player disease.

Dates and versions

hal-04285444 , version 1 (14-11-2023)

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Bassil Dekky, Fida Azar, Dominique Bonnier, Christine Monseur, Chiara Kalebić, et al.. ADAMTS12 is a stromal modulator in chronic liver disease. FASEB Journal, 2023, 37 (11), pp.e23237. ⟨10.1096/fj.202200692rrrr⟩. ⟨hal-04285444⟩
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