Podocyte expression of nonmuscle myosin heavy chain-IIA decreases in idiopathic nephrotic syndrome, especially in focal segmental glomerulosclerosis

BACKGROUND: Previous studies have identified significant associations between the development of idiopathic focal segmental glomerulosclerosis (FSGS) and MYH9 encoding nonmuscle myosin heavy chain-IIA (NMMHC-IIA). However, these studies focused only on the linkage of MYH9 polymorphisms and development of FSGS. There have been no reports on pathological changes of NMMHC-IIA in human glomerular diseases. Here we report on the precise localization of NMMHC-IIA in podocytes and changes in NMMHC-IIA expression in pathological states in rats and humans. METHODS: Immunocytochemical (immunofluorescence and immunoelectron microscopy) studies were performed to determine the precise localization of NMMHC-IIA. Expression levels of NMMHC-IIA were investigated in puromycin aminonucleoside (PAN)-treated rats; and expression levels of NMMHC-IIA and other podocyte-related proteins were investigated in glomeruli of patients with idiopathic FSGS and other heavy proteinuric glomerular diseases. RESULTS: NMMHC-IIA was located primarily at the cell body and primary processes of podocytes; this localization is distinct from other podocyte-related molecules causing hereditary FSGS. In PAN-treated rat kidneys, expression levels of NMMHC-IIA in podocytes decreased. Immunohistochemical analysis revealed that expression levels of NMMHC-IIA markedly decreased in idiopathic nephrotic syndrome, especially FSGS, whereas it did not change in other chronic glomerulonephritis showing apparent proteinuria. Changes in NMMHC-IIA expression were observed in glomeruli where expression of nephrin and synaptopodin was maintained. CONCLUSIONS: Considering previous genome-wide association studies and development of FSGS in patients with MYH9 mutations, the characteristic localization of NMMHC-IIA and the specific decrease in NMMHC-IIA expression in idiopathic nephrotic syndrome, especially FSGS, suggest the important role of NMMHC-IIA in the development of FSGS.