Modulation of the expression and activity of cathepsin S in reconstructed human skin by neohesperidin dihydrochalcone.

Autor: Sage J; LVMH-Recherche, F-45800 Saint Jean de Braye, France., Renault J; Université de Tours, Tours, France; INSERM, UMR 1100, Centre d'Etude des Pathologies Respiratoires, Team Mécanismes Protéolytiques dans l'Inflammation, F-37032 Tours, France., Domain R; Université de Tours, Tours, France; INSERM, UMR 1100, Centre d'Etude des Pathologies Respiratoires, Team Mécanismes Protéolytiques dans l'Inflammation, F-37032 Tours, France., Bojarski KK; Faculty of Chemistry, University of Gdańsk, Gdańsk 80-308, Poland., Chazeirat T; Université de Tours, Tours, France; INSERM, UMR 1100, Centre d'Etude des Pathologies Respiratoires, Team Mécanismes Protéolytiques dans l'Inflammation, F-37032 Tours, France., Saidi A; Université de Tours, Tours, France; INSERM, UMR 1100, Centre d'Etude des Pathologies Respiratoires, Team Mécanismes Protéolytiques dans l'Inflammation, F-37032 Tours, France., Leblanc E; LVMH-Recherche, F-45800 Saint Jean de Braye, France., Nizard C; LVMH-Recherche, F-45800 Saint Jean de Braye, France., Samsonov SA; Faculty of Chemistry, University of Gdańsk, Gdańsk 80-308, Poland., Kurfurst R; LVMH-Recherche, F-45800 Saint Jean de Braye, France., Lalmanach G; Université de Tours, Tours, France; INSERM, UMR 1100, Centre d'Etude des Pathologies Respiratoires, Team Mécanismes Protéolytiques dans l'Inflammation, F-37032 Tours, France., Lecaille F; Université de Tours, Tours, France; INSERM, UMR 1100, Centre d'Etude des Pathologies Respiratoires, Team Mécanismes Protéolytiques dans l'Inflammation, F-37032 Tours, France. Electronic address: fabien.lecaille@univ-tours.fr.
Jazyk: angličtina
Zdroj: Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2022 Mar; Vol. 107, pp. 97-112. Date of Electronic Publication: 2022 Feb 12.
DOI: 10.1016/j.matbio.2022.02.003
Abstrakt: Dysregulation of cathepsin S (Cat S), a cysteine protease involved in extracellular-matrix and basement membrane (BM) degradation, is a concomitant feature of several inflammatory skin diseases. Therefore, Cat S has been suggested as a potential therapeutic target. Flavonoids, which were identified as regulatory molecules of various proteolytic enzymes, exert beneficial effects on skin epidermis. Herein, thirteen flavonoid compounds were screened in vitro and in silico and neohesperidin dihydrochalcone (NHDC) was identified as a potent, competitive, and selective inhibitor (K i =8±1 µM) of Cat S. Furthermore, Cat S-dependent hydrolysis of nidogen-1, a keystone protein of BM architecture, as well elastin, collagens I and IV was impaired by NHDC, while both expression and activity of Cat S were significantly reduced in NHDC-treated human keratinocytes. Moreover, a reconstructed human skin model showed a significant decrease of both mRNA and protein levels of Cat S after NHDC treatment. Conversely, the expression of nidogen-1 was significantly increased. NHDC raised IL-10 expression, an anti-inflammatory cytokine, and mediated STAT3 signaling pathway, which in turn dampened Cat S expression. Our findings support that NHDC may represent a valuable scaffold for structural improvement and development of Cat S inhibitors to preserve the matrix integrity and favor skin homeostasis during inflammatory events.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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