Transforming growth factor-beta isoforms and glomerular injury in nephrotoxic nephritis

H M Wilson, A W M Minto, P A J Brown, L P Erwig, A J Rees

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background. Transforming growth factor-beta has three main isoforms (TGF-beta 1, TGF-beta 2, and TGF-beta 3) that have distinct but overlapping functions in immunity, inflammation, and tissue repair. TGF-beta 1 has been implicated in progressive renal scarring, but the roles of TGF-beta 2 and TGF-beta 3 are less clear. The purpose of this study was to characterize the expression of all three isoforms in nephrotoxic nephritis (NTN) in rats and to determine the effect of TGF-beta 3 infusions on injury because of its reported combined anti-inflammatory and antifibrotic effects.

Methods. TGF-beta 1,TGF-beta 2, and TGF-beta 3 expression was analyzed by immunohistochemistry and RNase protection assays. TGF-beta 3 was administered by osmotic minipumps at 2 mu g/day, a dose shown to alter glomerular macrophage function in vivo. Injury was assessed morphologically and functionally.

Results. The three TGF-beta isoforms showed a different distribution in normal rats and after the induction of nephritis. TGF-beta 1 was only detected in glomeruli of the most severely nephritic rats. TGF-beta 2 was found in glomerular neutrophils, whereas damaged podocytes expressed TGF-beta 3. Infusions of TGF-beta 3 did not reduce proteinuria over seven days after the induction of nephritis. They did, however, have a profound effect on glomerular macrophage number (7.76 +/- 4.1 in treated rats vs. 14.4 +/- 4.7 in controls, P < 0.02). The numbers of class II-positive macrophages were similar in the two groups, whereas class II-negative macrophages infiltrating glomeruli were significantly decreased (4.06 +/- 3.1 vs. 9.1 +/- 4.4, P < 0.02). TGF-beta did not influence the amount of glomerular matrix.

Conclusions. TGF-beta isoforms have different expressions and presumptively different roles in NTN. The infusion of pharmacological doses of TGF-beta 3 has profound effects on macrophages infiltrating nephritic glomeruli and reveals marked heterogeneity of infiltrating macrophages.

Original languageEnglish
Pages (from-to)2434-2444
Number of pages11
JournalKidney International
Volume57
Publication statusPublished - 2000

Keywords

  • nephrotoxic nephritis
  • macrophage
  • inflammation
  • tissue repair
  • progressive renal disease
  • TGF-BETA
  • EXPERIMENTAL GLOMERULONEPHRITIS
  • DIFFERENTIAL EXPRESSION
  • RAT-KIDNEY
  • EXTRACELLULAR-MATRIX
  • GROWTH-FACTOR-BETA-2
  • DISEASE
  • GENE
  • INTERLEUKIN-10
  • FACTOR-BETA-1

Cite this

Wilson, H. M., Minto, A. W. M., Brown, P. A. J., Erwig, L. P., & Rees, A. J. (2000). Transforming growth factor-beta isoforms and glomerular injury in nephrotoxic nephritis. Kidney International, 57, 2434-2444.

Transforming growth factor-beta isoforms and glomerular injury in nephrotoxic nephritis. / Wilson, H M ; Minto, A W M ; Brown, P A J ; Erwig, L P ; Rees, A J .

In: Kidney International, Vol. 57, 2000, p. 2434-2444.

Research output: Contribution to journalArticle

Wilson, HM, Minto, AWM, Brown, PAJ, Erwig, LP & Rees, AJ 2000, 'Transforming growth factor-beta isoforms and glomerular injury in nephrotoxic nephritis', Kidney International, vol. 57, pp. 2434-2444.
Wilson, H M ; Minto, A W M ; Brown, P A J ; Erwig, L P ; Rees, A J . / Transforming growth factor-beta isoforms and glomerular injury in nephrotoxic nephritis. In: Kidney International. 2000 ; Vol. 57. pp. 2434-2444.
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T1 - Transforming growth factor-beta isoforms and glomerular injury in nephrotoxic nephritis

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AU - Minto, A W M

AU - Brown, P A J

AU - Erwig, L P

AU - Rees, A J

PY - 2000

Y1 - 2000

N2 - Background. Transforming growth factor-beta has three main isoforms (TGF-beta 1, TGF-beta 2, and TGF-beta 3) that have distinct but overlapping functions in immunity, inflammation, and tissue repair. TGF-beta 1 has been implicated in progressive renal scarring, but the roles of TGF-beta 2 and TGF-beta 3 are less clear. The purpose of this study was to characterize the expression of all three isoforms in nephrotoxic nephritis (NTN) in rats and to determine the effect of TGF-beta 3 infusions on injury because of its reported combined anti-inflammatory and antifibrotic effects.Methods. TGF-beta 1,TGF-beta 2, and TGF-beta 3 expression was analyzed by immunohistochemistry and RNase protection assays. TGF-beta 3 was administered by osmotic minipumps at 2 mu g/day, a dose shown to alter glomerular macrophage function in vivo. Injury was assessed morphologically and functionally.Results. The three TGF-beta isoforms showed a different distribution in normal rats and after the induction of nephritis. TGF-beta 1 was only detected in glomeruli of the most severely nephritic rats. TGF-beta 2 was found in glomerular neutrophils, whereas damaged podocytes expressed TGF-beta 3. Infusions of TGF-beta 3 did not reduce proteinuria over seven days after the induction of nephritis. They did, however, have a profound effect on glomerular macrophage number (7.76 +/- 4.1 in treated rats vs. 14.4 +/- 4.7 in controls, P < 0.02). The numbers of class II-positive macrophages were similar in the two groups, whereas class II-negative macrophages infiltrating glomeruli were significantly decreased (4.06 +/- 3.1 vs. 9.1 +/- 4.4, P < 0.02). TGF-beta did not influence the amount of glomerular matrix.Conclusions. TGF-beta isoforms have different expressions and presumptively different roles in NTN. The infusion of pharmacological doses of TGF-beta 3 has profound effects on macrophages infiltrating nephritic glomeruli and reveals marked heterogeneity of infiltrating macrophages.

AB - Background. Transforming growth factor-beta has three main isoforms (TGF-beta 1, TGF-beta 2, and TGF-beta 3) that have distinct but overlapping functions in immunity, inflammation, and tissue repair. TGF-beta 1 has been implicated in progressive renal scarring, but the roles of TGF-beta 2 and TGF-beta 3 are less clear. The purpose of this study was to characterize the expression of all three isoforms in nephrotoxic nephritis (NTN) in rats and to determine the effect of TGF-beta 3 infusions on injury because of its reported combined anti-inflammatory and antifibrotic effects.Methods. TGF-beta 1,TGF-beta 2, and TGF-beta 3 expression was analyzed by immunohistochemistry and RNase protection assays. TGF-beta 3 was administered by osmotic minipumps at 2 mu g/day, a dose shown to alter glomerular macrophage function in vivo. Injury was assessed morphologically and functionally.Results. The three TGF-beta isoforms showed a different distribution in normal rats and after the induction of nephritis. TGF-beta 1 was only detected in glomeruli of the most severely nephritic rats. TGF-beta 2 was found in glomerular neutrophils, whereas damaged podocytes expressed TGF-beta 3. Infusions of TGF-beta 3 did not reduce proteinuria over seven days after the induction of nephritis. They did, however, have a profound effect on glomerular macrophage number (7.76 +/- 4.1 in treated rats vs. 14.4 +/- 4.7 in controls, P < 0.02). The numbers of class II-positive macrophages were similar in the two groups, whereas class II-negative macrophages infiltrating glomeruli were significantly decreased (4.06 +/- 3.1 vs. 9.1 +/- 4.4, P < 0.02). TGF-beta did not influence the amount of glomerular matrix.Conclusions. TGF-beta isoforms have different expressions and presumptively different roles in NTN. The infusion of pharmacological doses of TGF-beta 3 has profound effects on macrophages infiltrating nephritic glomeruli and reveals marked heterogeneity of infiltrating macrophages.

KW - nephrotoxic nephritis

KW - macrophage

KW - inflammation

KW - tissue repair

KW - progressive renal disease

KW - TGF-BETA

KW - EXPERIMENTAL GLOMERULONEPHRITIS

KW - DIFFERENTIAL EXPRESSION

KW - RAT-KIDNEY

KW - EXTRACELLULAR-MATRIX

KW - GROWTH-FACTOR-BETA-2

KW - DISEASE

KW - GENE

KW - INTERLEUKIN-10

KW - FACTOR-BETA-1

M3 - Article

VL - 57

SP - 2434

EP - 2444

JO - Kidney International

JF - Kidney International

SN - 0085-2538

ER -