| First Author | Möller-Hackbarth K | Year | 2021 |
| Journal | Kidney Int | Volume | 100 |
| Issue | 4 | Pages | 809-823 |
| PubMed ID | 34147551 | Mgi Jnum | J:317432 |
| Mgi Id | MGI:6852778 | Doi | 10.1016/j.kint.2021.05.036 |
| Citation | Moller-Hackbarth K, et al. (2021) Retinoic acid receptor responder1 promotes development of glomerular diseases via the Nuclear Factor-kappaB signaling pathway. Kidney Int 100(4):809-823 |
| abstractText | Inflammatory pathways are activated in most glomerular diseases but molecular mechanisms driving them in kidney tissue are poorly known. We identified retinoic acid receptor responder 1 (Rarres1) as a highly podocyte-enriched protein in healthy kidneys. Studies in podocyte-specific knockout animals indicated that Rarres1 was not needed for the normal development or maintenance of the glomerulus filtration barrier and did not modulate the outcome of kidney disease in a model of glomerulonephritis. Interestingly, we detected an induction of Rarres1 expression in glomerular and peritubular capillary endothelial cells in IgA and diabetic kidney disease, as well as in ANCA-associated vasculitis. Analysis of publicly available RNA data sets showed that the induction of Rarres1 expression was a common molecular mechanism in chronic kidney diseases. A conditional knock-in mouse line, overexpressing Rarres1 specifically in endothelial cells, did not show any obvious kidney phenotype. However, the overexpression promoted the progression of kidney damage in a model of glomerulonephritis. In line with this, conditional knock-out mice, lacking Rarres1 in endothelial cells, were partially protected in the disease model. Mechanistically, Rarres1 promoted inflammation and fibrosis via transcription factor Nuclear Factor-kappaB signaling pathway by activating receptor tyrosine kinase Axl. Thus, induction of Rarres1 expression in endothelial cells is a prevalent molecular mechanism in human glomerulopathies and this seems to have a pathogenic role in driving inflammation and fibrosis via the Nuclear Factor-kappaB signaling pathway. |
