Intercellular Signaling and Biomechanics of Podocytes and Endothelial Cells in FSGS
Abstract
The molecular mechanisms for glomerular cell crosstalk and regulatory inter-cellular feedback remain poorly understood. In experimental models of focal segmental glomerulosclerosis (FSGS), we described a novel hypothesis of glomerular endothelial cell and podocyte crosstalk where perturbations of microvascular homeostasis initiate mitochondrial stress and dysfunction of glomerular endothelial cells as well as loss of endothelial glycocalyx. This in turn results in subsequent podocyte depletion and irreversible sclerosis mediated by soluble endothelial cell secreted factors. We hypothesize that endothelial cell dysfunction mediates podocyte injury and loss through a mechanobiological pathway that can be therapeutically targeted. We will test this hypothesis with our micro engineered 3-Dglomerulus-on-chip platform in endothelial cells and podocytes derived from human induced pluripotent stem cell (hiPSC), and validate these findings in experimental mouse models of FSGS. Studies thus far show our ability to grow hiPSCs and to inhibit the production of stress secreted factors with RNAi intervention and novel small molecule antagonists.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1191230
Entities
People
- Evren Azeloglu
- Ilse Daehn
Organizations
- Icahn School of Medicine at Mount Sinai