Of these nine proteins, mutations in the genes encoding four of them (LAMB2, COL4A3, COL4A4, and COL4A5) cause glomerular disease in humans as well as in mice.
Genetic and pathological analyses of additional cases would clarify the role of LMX1B in glomerulopathy without systemic symptoms, which, together with nephropathy in NPS, can be designated as 'LMX1B nephropathy'.
Denys-Drash syndrome (DDS), caused by mutations in the WT1 gene affecting the third or second zinc finger, is characterized by a triad of glomerulopathy progressing rapidly to end-stage renal disease, male hermaphroditism, and Wilms tumor.
The WT1 gene encodes a zinc finger transcription factor involved in kidney and gonadal development and, when mutated, in the occurrence of kidney tumor and glomerular diseases.
Molecular studies of Lmx1b, combined with genetic and immunohistochemical investigation of different alpha chains of type IV collagen in the Lmx1b null mice kidney, a mouse model for NPS, have provided evidence that Lmx1b is involved in the pathogenesis of NPS glomerulopathy.
Several studies have identified gain-of-function mutations of <i>TRPC6</i> and report induced expression and enhanced channel activity of TRPC6 in association with glomerular diseases.
Increased calcium ion entry through the TRPC6 channel has been associated with the pathogenesis of heart and glomerular diseases, but its role in renal interstitial fibrosis is unknown.
Therefore, we provide evidence demonstrating the critical role of Ang II/TRPC6 axis in the control of glomeruli function, which is likely important for the development of glomerular diseases.