Endothelin A receptor activation on mesangial cells initiates Alport glomerular disease

Dufek B. Meehan D.T., Delimont D., Cheung L., Gratton M.A., Phillips G., Song W., Liu S., Cosgrove D.International Society of Nephrology, 2016

Normally, α5 laminins are highly expressed in the glomerular basement membranes (GBM).  In this article, the authors show that the mesangial filopodia in the GBM are depositing mesangial matrix proteins, including laminin 211, which activates focal adhesion kinase in glomerular podocytes, resulting in the activation of genes encoding proinflammatory cytokines and metalloproteinases through a nuclear factor kB–dependent signaling pathway, which drive the progression of glomerulonephritis. The authors test whether endothelial cell-derived endothelin-1 is up-regulated in Alport glomeruli and further elevated by hypertension. Endothelin A receptor activation on mesangial cells is a key event in the initiation of Alport glomerular disease in this model.

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