title: Podocyte expression of nonmuscle myosin heavy chain-IIA decreases in idiopathic nephrotic syndrome, especially in focal segmental glomerulosclerosis.
abstract: 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.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Miura
authors.forename: Hidetake
authors.initials: H
authors.lastname: Kurihara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Horita
authors.forename: Hiroko
authors.initials: H
authors.lastname: Chikamoto
authors.forename: Motoshi
authors.initials: M
authors.lastname: Hattori
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Harita
authors.forename: Haruko
authors.initials: H
authors.lastname: Tsurumi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kajiho
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sawada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kunishima
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekine
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D011507:Proteinuria / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains
keywords: focal segmental glomerulosclerosis; myh9; nonmuscle myosin heavy chain-IIA; podocyte; primary process