Rat mesangial cell hypertrophy in response to transforming growth factor-beta 1

Kidney Int. 1993 Nov;44(5):948-58. doi: 10.1038/ki.1993.336.

Abstract

Central features of progressive glomerular sclerosis are initial glomerular hypertrophy and subsequent accumulation of extracellular matrix proteins. Since TGF-beta 1 may play a key role in this glomerular response to injury, the present study sought to explore further TGF-beta 1 actions and regulated expression of its receptor in rat mesangial cells. The rat TGF-beta type II receptor (TGF-beta RII) homolog was cloned by screening a rat kidney cDNA library with a human TGF-beta RII cDNA probe, and sequenced. Expression of this receptor subtype in rat mesangial cells was then demonstrated by RNase protection assay, and by Northern blot analysis of poly (A)+ RNA, TGF-beta RII expression was down-regulated in cells treated with exogenous TGF-beta 1. Affinity cross linking studies demonstrated presence of this receptor on cell surface. Rat mesangial cells also expressed TGF-beta 1 and autoinduction by TGF-beta 1 was observed in the same cells, suggesting that this polypeptide may act in an autocrine fashion on mesangial cells, and that it may stimulate a positive autoamplification loop. TGF-beta 1 inhibited mesangial cell proliferation and stimulated significant overall protein and collagen production. Furthermore, mesangial cell size increased in response to chronic TGF-beta 1 treatment. These findings demonstrate that rat mesangial cells express key components of the TGF-beta system and raise the intriguing possibility that in the glomerular mesangium, TGF-beta 1 may not only induce extracellular matrix synthesis, but may also participate in the process of glomerular hypertrophy in response to injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Division / drug effects
  • DNA, Complementary / genetics
  • Gene Expression Regulation
  • Glomerular Mesangium / drug effects*
  • Glomerular Mesangium / pathology
  • Hypertrophy
  • Leucine / metabolism
  • Molecular Probes / genetics
  • Molecular Sequence Data
  • Proline / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Transforming Growth Factor beta / genetics
  • Thymidine / metabolism
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology*

Substances

  • DNA, Complementary
  • Molecular Probes
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Proline
  • Leucine
  • Thymidine