| First Author | Soloyan H | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 11414 |
| PubMed ID | 32651395 | Mgi Jnum | J:294288 |
| Mgi Id | MGI:6453523 | Doi | 10.1038/s41598-020-67588-0 |
| Citation | Soloyan H, et al. (2020) Glomerular endothelial cell heterogeneity in Alport syndrome. Sci Rep 10(1):11414 |
| abstractText | Glomerular endothelial cells (GEC) are a crucial component of the glomerular physiology and their damage contributes to the progression of chronic kidney diseases. How GEC affect the pathology of Alport syndrome (AS) however, is unclear. We characterized GEC from wild type (WT) and col4alpha5 knockout AS mice, a hereditary disorder characterized by progressive renal failure. We used endothelial-specific Tek-tdTomato reporter mice to isolate GEC by FACS and performed transcriptome analysis on them from WT and AS mice, followed by in vitro functional assays and confocal and intravital imaging studies. Biopsies from patients with chronic kidney disease, including AS were compared with our findings in mice. We identified two subpopulations of GEC (dim(tdT) and bright(tdT)) based on the fluorescence intensity of the Tek(tdT) signal. In AS mice, the bright(tdT) cell number increased and presented differential expression of endothelial markers compared to WT. RNA-seq analysis revealed differences in the immune and metabolic signaling pathways. In AS mice, dim(tdT) and bright(tdT) cells had different expression profiles of matrix-associated genes (Svep1, Itgbeta6), metabolic activity (Apom, Pgc1alpha) and immune modulation (Apelin, Icam1) compared to WT mice. We confirmed a new pro-inflammatory role of Apelin in AS mice and in cultured human GEC. Gene modulations were identified comparable to the biopsies from patients with AS and focal segmental glomerulosclerosis, possibly indicating that the same mechanisms apply to humans. We report the presence of two GEC subpopulations that differ between AS and healthy mice or humans. This finding paves the way to a better understanding of the pathogenic role of GEC in AS progression and could lead to novel therapeutic targets. |
