ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Abstract: FR-PO998

Glomerular Endothelial Cell Identity and Contribution to CKD in Alport Syndrome

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic


  • Sedrakyan, Sargis, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Soloyan, Hasmik, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Villani, Valentina, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Thornton, Matthew Edward, University of Southern California, Los Angeles, California, United States
  • Perin, Laura, Childrens Hospital Los Angeles, Los Angeles, California, United States

Group or Team Name

  • GOFARR laboratory for organ regenerative research and cell therapeutics

Many studies suggest that glomerular endothelial cell (GEC) injury plays a key role in the development of chronic kidney disease, but whether they contribute to pathogenesis and progression of Alport syndrome (AS) is not clearly established. In AS, a hereditary CKD characterized by the mutations in the collagen IVα3α4α5 protein, the major constituent of the glomerular basement membrane (GBM), we found morphological and biological alterations in GEC very early during disease progression and before the onset of heavy proteinuria. Thus, we hypothesized that in our model of CKD, GEC damage plays a key role.


To investigate our hypothesis we generated GEC specific (Tek-Cre driven) tdTomato reporter AS mice, harvested their glomeruli by the sieving method and isolated GEC by FACS. GEC were characterized and studied by flow cytometry analysis, PCR and WB at different time points along disease progression. GEC transcriptome profiling was performed by NGS on Illumina HiSeq 4000 and further analyzed by alignment of reads to Genecode M16 mouse genome. Differential gene expression analysis was performed post RUV normalization by BIOBASE and Ingenuity Pathway Analysis tools.


We identified two unique subsets of endothelial cells within the glomerulus of WT mice, and for the first time also in AS mice, which might present different functional roles during AS progression. We showed a significant increase in endothelial fenestration size, loss of glycocalyx integrity and alteration of VEGF signaling in GEC, early during progression and before the onset of proteinuria in AS mice. In addition, we identified differentially expressed genes involved in the angiogenic, stress response and metabolic regulatory pathways such as VEGF, PPAR, and FATp4.


In sum, our data indicate that GEC injury is an important early event that sets the stage for further progression and onset of proteinuria in Alport mice. Characterization of the transcriptional profile of GEC in AS mice could lead to the development of targeted new therapies for the treatment of CKD.


  • Private Foundation Support