In vitro studies on the roles of transforming growth factor-beta 1 in rat metanephric development

Kidney Int. 2001 May;59(5):1641-53. doi: 10.1046/j.1523-1755.2001.0590051641.x.

Abstract

Background: The development of the permanent kidney (metanephros) involves the interplay between both positive and negative regulatory molecules. Transforming growth factor-beta1 (TGF-beta 1) has previously been shown to negatively regulate ureteric duct growth. However, its potential role in nephron development and glomerulogenesis has been largely ignored.

Methods: In situ hybridization and reverse transcription-polymerase chain reaction were employed to examine the temporal and spatial localization of TGF-beta 1 mRNA and a TGF-beta type I receptor (activin-like receptor kinase-5; ALK-5) mRNA in developing rat metanephroi. The addition of exogenous TGF-beta 1 to rat metanephric organ culture at different time points was used to examine the role of TGF-beta 1 in ureteric duct growth and nephron development.

Results: TGF-beta 1 mRNA did not colocalize with ALK-5 mRNA. Instead, TGF-beta1 mRNA colocalized with the TGF-beta type II receptor mRNA. The addition of recombinant human TGF-beta 1 to rat metanephric organ culture at the beginning of the culture period inhibited total metanephric growth and the growth of the ureteric tree, resulting in a decrease in nephron number. Similarly, the addition of TGF-beta 1 to metanephroi after 48 hours of culture inhibited ureteric duct growth, decreasing nephron number. The addition of TGF-beta 1 at days 0 or 2 of culture promoted hypertrophy of the renal capsule.

Conclusions: These findings confirm that TGF-beta 1 inhibits ureteric duct growth and thereby nephron endowment in developing rat metanephroi in vitro. However, TGF-beta 1 does not appear to play a significant role in nephron development per se once the epithelial vesicle has formed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I*
  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • In Situ Hybridization
  • Kidney / drug effects
  • Kidney / embryology*
  • Kidney / physiology
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / embryology
  • Kidney Glomerulus / physiology
  • Male
  • Organ Culture Techniques
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / physiology
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology*

Substances

  • DNA Primers
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human
  • Tgfbr1 protein, rat