Thy1 glomerulonephritis induced in young lewis rats accelerates age-related glomerulosclerosis

Keith Nicol Stewart, P. Wilson, A. Minto, Alison Murray MacLeod, Paul Anthony James Brown, Moyra Elizabeth Glennie, Neva Elizabeth Haites, P. Whiting

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Age-related and disease-induced glomerulosclerosis (GS) in rats have both been well defined in a number of strains and experimental models, but the inter-relationship between the two is not clear. The present study was undertaken to compare the pattern of glomerular injury in these two types of GS. One- and two-shot Thy1 glomerulonephritis (GN) was induced at 2 months of age and followed for 12 months. At 12 months histological injury in proteinuric rats was characterized by segmental hyaline lesions. Two-shot Thy1 GN resulted in accelerated, but morphologically identical injury at 8 months. Histological lesions predictive of subsequent accelerated GS were evaluated at 1, 2, 4 and 6 months. In this regard, glomerular hypercellularity, rather than hypertrophy or matrix increase, was the most consistent histological index of later accelerated disease. The profibrotic cytokines transforming growth factor (TGF)-beta (1) and -beta (3) were localized distinctly to segmental hyaline lesions, but not to areas of matrix increase within the glomerular tuft. This study reveals that GS after Thy1 GN represents acceleration of an age-related disease, presents evidence for use of prolonged glomerular hypercellularity as the best histological index of future disease progression, and correlates the key lesion of GS in these animals, the segmental hyaline lesion, with the presence of TGF-beta peptides. Copyright (C) 2001 S. Karger AG, Basel.

Original languageEnglish
Pages (from-to)57-64
Number of pages7
JournalNephron Experimental Nephrology
Volume88
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • glomerulosclerosis
  • age
  • anti-Thy1 nephritis
  • transforming growth factor-beta
  • MESANGIAL PROLIFERATIVE NEPHRITIS
  • GROWTH-FACTOR
  • SEGMENTAL GLOMERULOSCLEROSIS
  • KIDNEY
  • EXPRESSION
  • PROGRESSION
  • NEPHROPATHY
  • ANTIBODIES
  • TGF-BETA-1
  • INSIGHTS

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