Modeling C3 glomerulopathies: C3 convertase regulation on an extracellular matrix surface.

ABSTRACT:

Introduction

C3 glomerulopathies (C3G) are ultra-rare complement-mediated diseases that lead to end-stage renal disease (ESRD) within 10 years of diagnosis in ~50% of patients. Overactivation of the alternative pathway (AP) of complement in the fluid phase and on the surface of the glomerular endothelial glycomatrix is the underlying cause of C3G. Although there are animal models for C3G that focus on genetic drivers of disease, in vivo studies of the impact of acquired drivers are not yet possible.

Methods

Here we present an in vitro model of AP activation and regulation on a glycomatrix surface. We use an extracellular matrix substitute (MaxGel) as a base upon which we reconstitute AP C3 convertase. We validated this method using properdin and Factor H (FH) and then assess

SUBMITTER: Pisarenka S 

PROVIDER: S-EPMC9947773 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature