title: Heminephrectomy causes the progression of glomerulosclerosis and apoptosis in high IgA strain ddY mice.
abstract: BACKGROUND
  The reduction in nephrons in IgA nephropathy is critical to the prognosis of this disease. However, the immunopathological mechanism of the modifications seen in glomerular lesions is not clear. We thus investigated the influence of nephron reduction by heminephrectomy on renal lesions in a high immunoglobulin A inbred strain of ddY mouse (HIGA mouse), which shows progressive mesangial sclerosis with elevated renal expression of transforming growth factor (TGF)-beta.
  
  
  METHODS
  Five-week-old HIGA mice were heminephrectomized (Nx), and were evaluated in comparison with a sham-operated group (S) at 40 weeks old. Histological findings, immunoglobulin depositions (IgG, IgA, and IgM), and expressions of cytokine and extracellular matrix proteins (TGF-beta, fibronectin, collagen type I and IV) were analysed. PCNA and TUNEL stainings were performed with electron microscopic detection of apoptosis. Tissue renin-angiotensin systems (RAS) were also investigated by real-time quantitative RT-PCR.
  
  
  RESULTS
  In the Nx group, the glomerular tuft area and ratio of mesangial matrix area per tuft were significantly increased, and the glomerular cell count per tuft area was significantly decreased. Glomerular immunoglobulin deposits of IgG, IgA, and IgM in Nx were all significantly expanded in the paramesangium. The glomerular expressions of TGF-beta and the extracellular matrix proteins were significantly increased in Nx mice. In contrast to the significant decrease of PCNA-positive cells, TUNEL-positive cells were significantly increased in Nx. Angiotensin-converting enzyme (ACE) was significantly increased in the renal cortex of Nx.
  
  
  CONCLUSIONS
  Simple heminephrectomy, other than 5/6 renal ablation, of HIGA mice may be a potential model for research into the progressive glomerulosclerosis of human IgA nephropathy. The pathological role of apoptosis is apparently involved in these disease processes, possibly through upregulated RAS.
authors.affiliation: Nephrology Division, Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, 54 Shogo-in Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kusano
authors.forename: Eri
authors.initials: E
authors.lastname: Muso
authors.forename: Takahiko
authors.initials: T
authors.lastname: Ono
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Nogaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Nomura
authors.forename: Toshiya
authors.initials: T
authors.lastname: Takeda
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyawaki
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumori
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Shigetake
authors.initials: S
authors.lastname: Sasayama
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000276:immunology / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009392:Nephrectomy; D012084:Renin-Angiotensin System / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D007070:Immunoglobulin A; D016212:Transforming Growth Factor beta