Titre :

The Accumulation of Heparan Sulfate S-Domains in Kidney Transthyretin Deposits Accelerates Fibril Formation and Promotes Cytotoxicity

Auteur(s) :

Kameyama, Hirokazu [Auteur]
Uchimura, Kenji [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Nagoya University
Yamashita, Taro [Auteur]
Kuwabara, Kaori [Auteur]
Mizuguchi, Mineyuki [Auteur]
Hung, Shang-Cheng [Auteur]
Okuhira, Keiichiro [Auteur]
Masuda, Tomohiro [Auteur]
Kosugi, Tomoki [Auteur]
Ohgita, Takashi [Auteur]
Saito, Hiroyuki [Auteur]
Ando, Yukio [Auteur]
Nishitsuji, Kazuchika [Auteur]

Titre de la revue :

The American journal of pathology

Nom court de la revue :

Am. J. Pathol.

Numéro :

189

Pagination :

308-319

Éditeur :

Elsevier Inc

Date de publication :

2019-02-01

ISSN :

0002-9440

Discipline(s) HAL :

Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

The highly sulfated domains of heparan sulfate (HS), alias HS S-domains, are made up of repeated trisulfated disaccharide units [iduronic acid (2S)-glucosamine (NS, 6S)] and are selectively remodeled by extracellular ...
Lire la suite >The highly sulfated domains of heparan sulfate (HS), alias HS S-domains, are made up of repeated trisulfated disaccharide units [iduronic acid (2S)-glucosamine (NS, 6S)] and are selectively remodeled by extracellular endoglucosamine 6-sulfatases (Sulfs). Although HS S-domains are critical for signal transduction of several growth factors, their roles in amyloidoses are not yet fully understood. Herein, we found HS S-domains in the kidney of a patient with transthyretin amyloidosis. In in vitro assays with cells stably expressing human Sulfs, heparin, a structural analog of HS S-domains, promoted aggregation of transthyretin in an HS S-domain–dependent manner. Interactions of cells with transthyretin fibrils and cytotoxicity of these fibrils also depended on HS S-domains at the cell surface. Furthermore, glypican-5, encoded by the susceptibility gene for nephrotic syndrome GPC5, was found to be accumulated in the transthyretin amyloidosis kidney. Our study, thus, provides a novel insight into the pathologic roles of HS S-domains in amyloidoses, and we propose that enzymatic remodeling of HS chains by Sulfs may offer an effective approach to inhibiting formation and cytotoxicity of amyloid fibrils.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Diversité structurale des héparanes sulfates et régulation de la réponse inflammatoire

Date de dépôt :

2020-12-14T10:15:24Z
2020-12-18T15:17:58Z