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Heminephrectomy causes the progression of glomerulosclerosis and apoptosis in high IgA strain of ddY (HIGA) mice
Author(s) -
Kusano H,
Miyawaki S,
Yoshida H,
Ono T,
Muso E,
Sasayama S
Publication year - 2001
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1046/j.1440-1797.2001.00002.x
Subject(s) - medicine , glomerulosclerosis , endocrinology , nephron , nephropathy , glomerulus , glomerulonephritis , proteinuria , kidney , diabetes mellitus
Background: The nephron reduction in IgA nephropathy is critical for the newly established prognosis of this disease. A high immunoglobulin A inbred strain of ddY mouse (HIGA mouse) showed progressive mesangial sclerosis with elevated renal expression of transforming growth factor (TGF)‐β, 1 however, the progression of the renal lesion of this mouse is relatively mild with rare association of active crescentic glomerulonephritis. However, although nephron reduction causes progressive renal injury, the modifications of glomerular lesions by nephron reduction are dependent upon the pathological background of each strain. Thus, we investigated the influence of nephron reduction by heminephrectomy on the renal lesions of the HIGA mouse. Methods: Five‐week‐old HIGA mice were heminephrectomized (Nx), and were evaluated in comparison with a sham‐operated group (S) at 40 weeks old. Measurements of renal function, blood pressure and serum levels of immunoglobulins (IgG, IgA, and IgM) were performed. Histological findings, including glomerular enlargement, matrix expansion, immunoglobulin depositions (IgG, IgA, and IgM), expressions of cytokines (TGF‐β, TNF‐α, and IL‐6) and extracellular matrix proteins were analysed. PCNA and TUNEL stainings were performed. In addition, mRNA expressions of renin‐angiotensin systems (RAS; angiotensinogen and angiotensin converting enzyme (ACE)) were also investigated. Results: The physiological and serological data showed no significant difference between Nx and S. In Nx, the glomerular tuft area and ratio of mesangial matrix area for one tuft were significantly increased and glomerular IgG and IgM deposits were significantly expanded in the paramesangium. However, IgA was not significantly increased. The glomerular expressions of cytokines (TGF‐β, TNF‐α, and IL‐6) and extracellular matrix proteins (fibronectin, collagen type I and IV) were significantly increased in this group. In contrast to the significant decrease of PCNA‐positive cells, TUNEL‐positive cells were significantly increased in Nx. The total mRNA expression of ACE was also significantly increased in the renal cortex of Nx. Conclusion: Heminephrectomy of HIGA mice may be a potential model for the research into the progressive glomerulosclerosis of human IgA nephropathy. The pathological role of apoptosis is apparently involved in these disease processes, possibly through up‐regulated RAS.