title: Early-onset podocyte injury and glomerular sclerosis in osborne-mendel rats.
abstract: Progressive glomerular injury associated with early-onset proteinuria was investigated in male Osborne-Mendel (OM) rats aged 5 to 20 weeks. Age-matched male Fischer 344 (F344) rats were used for comparison. OM rats developed mild hypertension and selective proteinuria (albuminuria) from 5 weeks of age, and non-selective proteinuria from 7 weeks of age. Light microscopy of OM kidney revealed hyaline droplets in the podocyte at 5 weeks of age and vacuolation of podocytes and adhesion of the capillary loop to the Bowman's capsule at 7 weeks of age. Segmental glomerulosclerosis developed in OM rats from 15 weeks of age, and global sclerosis appeared at 20 weeks of age. Desmin, a marker of podocye injury, was expressed in podocytes from 10 weeks of age, and the intensity of expression increased with age. Ultrastructurally, damage to podocytes such as effacement of foot processes, decreasing number of filtration slits, and rearrangement of the actin cytoskeleton were observed from 5 weeks of age in OM rat. Glomerular volume in OM rats increased with age and was consistently higher than in age-matched F344 rats. The number of WT-1-positive podocytes and vimentin-positive podocyte area were lower in OM rats and decreased with age. These findings suggest that glomerulonephropathy in male OM rats is associated with glomerular hypertrophy, progressive podocytopathy, and a reduction in podocyte number and area. Renal injury in OM rats was associated with development of early-onset proteinuria and was more progressive than in age-matched F344 rats.
authors.affiliation: Research Institute of Biosciences, Azabu University, Kanagawa, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Yasuno
authors.forename: Shoko
authors.initials: S
authors.lastname: Ishihara
authors.forename: Rio
authors.initials: R
authors.lastname: Saito
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kato
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Tomoshige
authors.initials: T
authors.lastname: Baba
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kawano
authors.forename: Kikumi
authors.initials: K
authors.lastname: Ogihara
authors.forename: Junichi
authors.initials: J
authors.lastname: Kamiie
authors.forename: Kinji
authors.initials: K
authors.lastname: Shirota
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure; D050476:Bowman Capsule / Q000473:pathology; D002448:Cell Adhesion; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013045:Species Specificity