Morin Acts as a USP7 Inhibitor to Hold Back the Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes in a "Prickle1-mTORC2" Dependent Manner.

The aim of this study is to investigate the effect and detailed mechanisms of morin, an anti-arthritis compound widely distributed in foods of plant origin, on the pathological migration of fibroblast-like synoviocytes (FLS).The migration of FLS collected from arthritis rats and MH7A cells is induced by platelet-derived growth factor, and ...
an arthritis model in rats is established by Freund's complete adjuvant. The results show that morin remarkably restrains FLS migration but slightly affects FLS apoptosis and proliferation. Moreover, in the progression of FLS migration, focal adhesion (FA) turnover is inhibited by morin via lowering the activation of Paxillin and focal adhesion kinase (FAK) and internalization of integrin ?1. Morin disrupts the formation of mTOR complex 2 (mTORC2) and the activation of AKT (S473) and PKC? (S657), and MHY1485 reverses morin-limited FLS migration. Of note, the protein stability of Prickle1, a binding factor of Rictor, is reduced by morin, and MG132 but not Baf A1 shows a repressive effect. Finally, the target protein is identified as ubiquitin-specific protease 7 (USP7) but not USP9X. USP7 overexpressing plasmid weakens morin-affected protein and ubiquitination of Prickle1, and mechanisms are confirmed in vivo by using an overexpressing plasmid and inhibitor.Morin restricts FLS migration and arthritis by intervening in "USP7-Prickle1-mTORC2" signaling and FA turnover.
Mesh Terms:
Animals, Arthritis, Rheumatoid, Cell Movement, Cells, Cultured, Female, Flavonoids, Focal Adhesions, Humans, LIM Domain Proteins, Mechanistic Target of Rapamycin Complex 2, Rats, Wistar, Synoviocytes, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Ubiquitin-Specific Peptidase 7, Ubiquitination
Mol Nutr Food Res
Date: Dec. 01, 2020
Download Curated Data For This Publication
234548
Switch View:
  • Interactions 2