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

Yasuhiko Ito1, Roel Goldschmeding, Hirotake Kasuga

  • 1Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.

American Journal of Physiology. Renal Physiology
|June 26, 2010
PubMed

Insights

Transforming growth factor-beta (TGF-β) and connective tissue growth factor (CTGF) are key in kidney development and fibrosis. Their coordinated expression in glomerulogenesis and disease suggests a role in kidney health and disease progression.

Area of Science:

  • Nephrology and Developmental Biology
  • Molecular Biology and Cell Signaling
  • Pathology and Fibrosis Research

Background:

  • Transforming growth factor-beta (TGF-β) isoforms (TGF-β1, TGF-β2, TGF-β3) regulate wound repair and fibrosis.
  • Connective tissue growth factor (CTGF) is stimulated by TGF-β and implicated in fibrotic disorders, but its role alongside TGF-β in normal kidney development is unclear.

Purpose of the Study:

  • To investigate the expression patterns and relationship between CTGF and TGF-β isoforms during rat and human kidney development (glomerulogenesis).
  • To compare CTGF and TGF-β isoform expression in normal adult glomeruli versus various human glomerulopathies.

Main Methods:

  • Comparative analysis of messenger RNA (mRNA) and protein expression of CTGF and TGF-β isoforms.
  • Utilized rat and human kidney tissues from different developmental stages and disease states.
  • Examined expression in normal adult glomeruli, glomerulonephritis, diabetic nephropathy, and IgA nephropathy.

Main Results:

  • CTGF mRNA appears in early glomerular precursors (comma- and S-shaped stages) and peaks in differentiating glomerular epithelial cells during capillary loop and maturing stages, coinciding with all TGF-β isoforms.
  • In normal adult glomeruli, CTGF expression is restricted to podocytes, correlating with TGF-β2 and TGF-β3 but not TGF-β1.
  • Coexpression of TGF-β1 and CTGF (with TGF-β2, TGF-β3) occurs in podocytes in proliferative glomerulonephritis and in mesangial cells in diabetic nephropathy and IgA nephropathy.

Conclusions:

  • Coordinated expression of TGF-β isoforms and CTGF is likely involved in normal kidney development (glomerulogenesis).
  • This coordinated expression may also be crucial for maintaining adult kidney structure and function.
  • Sustained overexpression of TGF-β1 and CTGF is associated with severe kidney diseases like glomerulonephritis and glomerulosclerosis.

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