Intravital imaging reveals glomerular capillary distension and endothelial and immune cell activation early in Alport syndrome.

ABSTRACT: Alport syndrome (AS) is a genetic disorder caused by mutations in type IV collagen that lead to defective glomerular basement membrane, glomerular filtration barrier (GFB) damage, and progressive chronic kidney disease. While the genetic basis of AS is well known, the molecular and cellular mechanistic details of disease pathogenesis have been elusive, hindering the development of mechanism-based therapies. Here, we performed intravital multiphoton imaging of the local kidney tissue microenvironment in a X-linked AS mouse model to directly visualize the major drivers of AS pathology. Severely distended glomerular capillaries and aneurysms were found accompanied by numerous microthrombi, increased glomerular endothelial surface layer (glycocalyx) and immune cell homing, GFB albumin leakage,

SUBMITTER: Gyarmati G 

PROVIDER: S-EPMC8765042 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature