A 3D tri-culture system reveals that activin receptor-like kinase 5 and connective tissue growth factor drive human glomerulosclerosis.

ABSTRACT: Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GECs), podocytes, and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis. GECs form a lumenized vascular network, which regresses in response to TGFβ. MCs respond to TGFβ by forming glomerulosclerotic-like nodules with matrix deposition. TGFβ treatment of podocytes does not alter cell morphology but increases connective tissue growth factor (CTGF)

SUBMITTER: Waters JP 

PROVIDER: S-EPMC6309868 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature