We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Plasma from a case of recurrent idiopathic FSGS perturbs non-muscle myosin IIA (MYH9 protein) in human podocytes.
- Authors
Babayeva, Sima; Miller, Michelle; Zilber, Yulia; Kares, Reyhan; Bernard, Chantale; Bitzan, Martin; Goodyer, Paul; Torban, Elena
- Abstract
The MYH9 gene encodes a non-muscle myosin IIA heavy chain (NMMHC-IIA) expressed in podocytes. Heterozygous MYH9 mutations cause a set of overlapping syndromes characterized by variable degrees of deafness, morphologic abnormalities of platelets and focal segmental glomerulosclerosis (FSGS) with progressive renal dysfunction. Similar glomerular lesions are seen in a variety of nephropathies, including an idiopathic form of FSGS in children which recurs in renal allografts, implying a circulating factor that affects glomerular podocyte biology. It is unknown whether NMMHC-IIA is perturbed in the idiopathic form of FSGS. We describe a pediatric patient with typical idiopathic FSGS, in whom proteinuria recurred within hours of deceased donor renal transplantation but who responded to plasmapheresis. We demonstrate in vitro that plasmapheresis effluent from our patient rapidly decreased cultured podocyte levels of the phosphorylated myosin light chain (MLC) that mediates NMMHC-IIA binding to actin and induced dispersion of NMMHC-IIA from its usual position along actin stress fibers. FSGS plasma also caused dispersion of slit diaphragm proteins (nephrin and podocin) and vinculin-positive focal adhesion complexes. Our observations suggest that the putative circulating factor in idiopathic FSGS disrupts normal NMMHC-IIA function in podocytes and might contribute to the pathogenesis of recurrent FSGS in other children.
- Subjects
TREATMENT of glomerulonephritis; ANALYSIS of variance; APOPTOSIS; CELL culture; ELECTRON microscopy; EPITHELIAL cells; FLUORESCENT antibody technique; GENE expression; IMMUNOASSAY; KIDNEY glomerulus; KIDNEY transplantation; GENETIC mutation; MYOSIN; PLASMAPHERESIS; PROTEINURIA; T-test (Statistics)
- Publication
Pediatric Nephrology, 2011, Vol 26, Issue 7, p1071
- ISSN
0931-041X
- Publication type
Article
- DOI
10.1007/s00467-011-1831-z