Selective Binding of Heparin/Heparan Sulfate Oligosaccharides to Factor H and Factor H-Related Proteins: Therapeutic Potential for C3 Glomerulopathies.
Atypical Hemolytic Uremic Syndrome
/ blood
Cells, Cultured
Complement Activation
Complement C3b
/ metabolism
Complement Factor H
/ metabolism
Complement System Proteins
/ metabolism
Endothelial Cells
/ metabolism
Heparin
/ analogs & derivatives
Heparitin Sulfate
/ metabolism
Humans
Kidney Glomerulus
/ metabolism
Protein Binding
/ drug effects
Signal Transduction
/ drug effects
complement
complement 3 glomerulopathy
factor H (FH)
factor H-related protein
heparan sulfate (HS)
heparin
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
05
03
2021
accepted:
02
08
2021
entrez:
7
9
2021
pubmed:
8
9
2021
medline:
27
10
2021
Statut:
epublish
Résumé
Complement dysregulation is characteristic of the renal diseases atypical hemolytic uremic syndrome (aHUS) and complement component 3 glomerulopathy (C3G). Complement regulatory protein Factor H (FH) inhibits complement activity, whereas FH-related proteins (FHRs) lack a complement regulatory domain. FH and FHRs compete for binding to host cell glycans, in particular heparan sulfates (HS). HS is a glycosaminoglycan with an immense structural variability, where distinct sulfation patterns mediate specific binding of proteins. Mutations in FH, FHRs, or an altered glomerular HS structure may disturb the FH : FHRs balance on glomerular endothelial cells, thereby leading to complement activation and the subsequent development of aHUS/C3G. In this study, we aimed to identify specific HS structures that could specifically compete off FHRs from HS glycocalyx (HS
Identifiants
pubmed: 34489931
doi: 10.3389/fimmu.2021.676662
pmc: PMC8416517
doi:
Substances chimiques
CFHR5 protein, human
0
Complement C3b
80295-43-8
Complement Factor H
80295-65-4
Heparin
9005-49-6
Complement System Proteins
9007-36-7
Heparitin Sulfate
9050-30-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
676662Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK110023
Pays : United States
Informations de copyright
Copyright © 2021 Loeven, Maciej-Hulme, Yanginlar, Hubers, Kellenbach, de Graaf, van Kuppevelt, Wetzels, Rabelink, Smith and van der Vlag.
Déclaration de conflit d'intérêts
Author EK was employed by company Aspen API. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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