Expression patterns of connective tissue growth factor and of TGF-β isoforms during glomerular injury recapitulate glomerulogenesis

Yasuhiko Ito, Roel Goldschmeding, Hirotake Kasuga, Nike Claessen, Masahiro Nakayama, Yukio Yuzawa, Akiho Sawai, Seiichi Matsuo, Jan J. Weening, Jan Aten

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Transforming growth factor (TGF)-β1, -β2, and -β3 are involved in control of wound repair and development of fibrosis. Connective tissue growth factor (CTGF) expression is stimulated by all TGF-β isoforms and is abundant in glomerulosclerosis and other fibrotic disorders. CTGF is hypothesized to mediate profibrotic effects of TGF-β1 or to facilitate interaction of TGF-β1 with its receptor, but its interactions with TGF-β isoforms in nonpathological conditions are unexplored so far. Tissue repair and remodeling may recapitulate gene transcription at play in organogenesis. To further delineate the relationship between CTGF and TGF-β, we compared expression patterns of CTGF and TGF-β isoforms in rat and human glomerulogenesis and in various human glomerulopathies. CTGF mRNA was present in the immediate precursors of glomerular visceral and parietal epithelial cells in the comma- and S-shaped stages, but not in earlier stages of nephron development. During the capillary loop and maturing glomerular stages and simultaneous with the presence of TGF-β1, -β2, and -β3 protein, CTGF mRNA expression was maximal and present only in differentiating glomerular epithelial cells. CTGF protein was also present on precursors of mesangium and glomerular endothelium, suggesting possible paracrine interaction. Concomitant with the presence of TGF-β2 and -β3 protein, and in the absence of TGF-β1, CTGF mRNA and protein expression was restricted to podocytes in normal adult glomeruli. However, TGF-β1 and CTGF were again coexpressed, often with TGF-β2 and -β3, in particular in podocytes in proliferative glomerulonephritis and also in mesangial cells in diabetic nephropathy and IgA nephropathy (IgA NP). Coordinated expression of TGF-β isoforms and of CTGF may be involved in normal glomerulogenesis and possibly in maintenance of glomerular structure and function at adult age. Prolonged overexpression of TGF-β1 and CTGF is associated with development of severe glomerulonephritis and glomerulosclerosis.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume299
Issue number3
DOIs
Publication statusPublished - 01-09-2010

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Connective Tissue Growth Factor
Transforming Growth Factors
Protein Isoforms
Wounds and Injuries
Podocytes
Glomerulonephritis
Messenger RNA
Proteins
Glomerular Mesangium
Mesangial Cells
Organogenesis
Nephrons
Diabetic Nephropathies

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Ito, Yasuhiko ; Goldschmeding, Roel ; Kasuga, Hirotake ; Claessen, Nike ; Nakayama, Masahiro ; Yuzawa, Yukio ; Sawai, Akiho ; Matsuo, Seiichi ; Weening, Jan J. ; Aten, Jan. / Expression patterns of connective tissue growth factor and of TGF-β isoforms during glomerular injury recapitulate glomerulogenesis. In: American Journal of Physiology - Renal Physiology. 2010 ; Vol. 299, No. 3.
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abstract = "Transforming growth factor (TGF)-β1, -β2, and -β3 are involved in control of wound repair and development of fibrosis. Connective tissue growth factor (CTGF) expression is stimulated by all TGF-β isoforms and is abundant in glomerulosclerosis and other fibrotic disorders. CTGF is hypothesized to mediate profibrotic effects of TGF-β1 or to facilitate interaction of TGF-β1 with its receptor, but its interactions with TGF-β isoforms in nonpathological conditions are unexplored so far. Tissue repair and remodeling may recapitulate gene transcription at play in organogenesis. To further delineate the relationship between CTGF and TGF-β, we compared expression patterns of CTGF and TGF-β isoforms in rat and human glomerulogenesis and in various human glomerulopathies. CTGF mRNA was present in the immediate precursors of glomerular visceral and parietal epithelial cells in the comma- and S-shaped stages, but not in earlier stages of nephron development. During the capillary loop and maturing glomerular stages and simultaneous with the presence of TGF-β1, -β2, and -β3 protein, CTGF mRNA expression was maximal and present only in differentiating glomerular epithelial cells. CTGF protein was also present on precursors of mesangium and glomerular endothelium, suggesting possible paracrine interaction. Concomitant with the presence of TGF-β2 and -β3 protein, and in the absence of TGF-β1, CTGF mRNA and protein expression was restricted to podocytes in normal adult glomeruli. However, TGF-β1 and CTGF were again coexpressed, often with TGF-β2 and -β3, in particular in podocytes in proliferative glomerulonephritis and also in mesangial cells in diabetic nephropathy and IgA nephropathy (IgA NP). Coordinated expression of TGF-β isoforms and of CTGF may be involved in normal glomerulogenesis and possibly in maintenance of glomerular structure and function at adult age. Prolonged overexpression of TGF-β1 and CTGF is associated with development of severe glomerulonephritis and glomerulosclerosis.",
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Expression patterns of connective tissue growth factor and of TGF-β isoforms during glomerular injury recapitulate glomerulogenesis. / Ito, Yasuhiko; Goldschmeding, Roel; Kasuga, Hirotake; Claessen, Nike; Nakayama, Masahiro; Yuzawa, Yukio; Sawai, Akiho; Matsuo, Seiichi; Weening, Jan J.; Aten, Jan.

In: American Journal of Physiology - Renal Physiology, Vol. 299, No. 3, 01.09.2010.

Research output: Contribution to journalArticle

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T1 - Expression patterns of connective tissue growth factor and of TGF-β isoforms during glomerular injury recapitulate glomerulogenesis

AU - Ito, Yasuhiko

AU - Goldschmeding, Roel

AU - Kasuga, Hirotake

AU - Claessen, Nike

AU - Nakayama, Masahiro

AU - Yuzawa, Yukio

AU - Sawai, Akiho

AU - Matsuo, Seiichi

AU - Weening, Jan J.

AU - Aten, Jan

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