Inflammatory molecules in the glomerular endothelium in mild IgA-Nephropathy identified by single-cell and spatial transcriptome

Immunoglobulin A nephropathy (IgA-N) is a primary glomerulonephritis characterized by mesangial cell proliferation and expansion. It still leads to end-stage renal disease over the long course of the disease in many patients. Although glomerular endothelial cells (GE) have been implicated in the pathogenesis of IgA-N, their role remains poorly understood. We conducted single-cell and spatial transcriptomic analysis using human specimens with mild IgA-N compared with normal. We observed the significantly higher expression of several inflammation-associated molecules which have been reported and not reported to be involved in IgA-N pathogenesis, respectively. Furthermore, we show that several important molecules were also highly expressed in GE of IgA-N at protein level by tissue immunostaining. Our analysis suggests that the characteristic pathways identified in GE that involve these molecules are associated with the progression of IgA-N. These findings offer important insights on both the pathogenesis of IgA-N and its treatment at an early stage.