Role of Mesangial-Podocytic-Tubular Cross-Talk in IgA Nephropathy

Summary: IgA nephropathy (IgAN), a common primary glomerulonephritis worldwide, is associated with a substantial risk of progression to end-stage renal failure. The disease runs a highly variable clinical course with frequent involvement of tubulointerstitial damage. A subgroup of IgAN with proximal tubular epithelial cells (PTECs) and tubulointerstitial damage often is associated with rapid progression to end-stage renal failure. Human mesangial cell-derived mediators lead to podocyte and tubulointerstitial injury via mesangial-podocytic-tubular cross-talk. Although mesangial-podocytic communication plays a pathogenic role in podocytic injury, the implication of a podocyte-PTEC cross-talk pathway in the progression of tubulointerstitial injury in IgAN should not be underscored. We review the role of mesangial-podocytic-tubular cross-talk in the progression of IgAN. We discuss how podocytopathy in IgAN promotes subsequent PTEC dysfunction and whether tubulointerstitial injury affects the propagation of podocytic injury in IgAN. A thorough understanding of the cross-talk mechanisms among mesangial cells, podocytes, and PTECs may lead to better design of potential therapeutic options for IgAN.