Organoid-on-a-chip model of human ARPKD reveals mechanosensing pathomechanisms for drug discovery.

ABSTRACT: Organoids serve as a novel tool for disease modeling in three-dimensional multicellular contexts. Static organoids, however, lack the requisite biophysical microenvironment such as fluid flow, limiting their ability to faithfully recapitulate disease pathology. Here, we unite organoids with organ-on-a-chip technology to unravel disease pathology and develop therapies for autosomal recessive polycystic kidney disease. PKHD1-mutant organoids-on-a-chip are subjected to flow that induces clinically relevant phenotypes of distal nephron dilatation. Transcriptomics discover 229 signal pathways that are not identified by static models. Mechanosensing molecules, RAC1 and FOS, are identified as potential therapeutic targets and validated by patient kidney samples. On the basis of this insigh

SUBMITTER: Hiratsuka K 

PROVIDER: S-EPMC9491724 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature