title: Advanced glomerulosclerosis is reversible in nephrotic mice.
abstract: Advanced glomerulosclerosis, a common hallmark of chronic renal diseases (CRD) is believed to be irreversible, and it is thought that glomerular hyperfiltration and hypertrophy may participate in its pathogenesis. We demonstrate here that glomerulosclerosis is "reversible" in an animal model. We used nephrotic ICGN (nep/nep) mice which showed a rapid progression of glomerulosclerosis, accompanied by histological findings for glomerular hyperfiltration. It is known that ureter ligation reduces glomerular filtration in ligated kidneys. When ureter ligation was applied to our model, glomerulosclerosis (characterized by myofibroblast hyperplasia and over-accumulated matrix protein) weakened in conjunction with suppressed glomerular hypertrophy. During this process, glomerular myofibroblasts showed apoptotic cell death after unilateral ureter ligation (UUO) treatment. Our results suggest that inhibition of glomerular filtration in sclerotic tufts may cause glomerular remodeling through the modulation of molecular and cellular sclerogenesis.
authors.affiliation: Division of Functional Diagnostic Imaging, Osaka University Medical School, 2-2-D11 Yamadaoka, Suita City, Osaka 565-0871, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mizuno-Horikawa
authors.forename: S
authors.initials: S
authors.lastname: Mizuno
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: T
authors.initials: T
authors.lastname: Kurosawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006984:Hypertrophy / Q000473:pathology / Q000628:therapy; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008026:Ligation; D051379:Mice; D008817:Mice, Mutant Strains; D012598:Sclerosis; D014513:Ureter
chemical_list: D005353:Fibronectins