Effects of hypertonic stress on transforming growth factor-beta activity in normal rat kidney cells

Kidney Int. 1998 Jun;53(6):1654-60. doi: 10.1046/j.1523-1755.1998.00903.x.


Hypertonicity is known to modulate the expression of some genes and the action of several cytokines. We evaluated whether hypertonicity would increase the expression and/or activity of transforming growth factor-beta (TGF-beta) in normal rat kidney (NRK) cells. The bioassay for TGF-beta showed that mature TGF-beta activity was significantly increased when the cells were cultured in a hypertonic medium (500 mOsm/kg). Comparing to the isotonic medium, hypertonicity accelerated the increase in TGF-beta activity during the initial 24 hours after changing the medium. The activity was increased as the medium osmolality increased from 300 to 500 mOsm/kg. Raffinose was found to be the most effective in increasing TGF-beta activity. NaCl, glucose, and mannitol also increased TGF-beta activity. In contrast, total TGF-beta (mature and latent) activity and TGF-beta mRNA abundance did not change significantly, suggesting that hypertonicity activated TGF-beta without affecting the synthesis of TGF-beta. To determine whether collagen synthesis was increased by hypertonicity, we examined [3H] proline incorporation into NRK cells cultured in hypertonic medium. Proline incorporation increased in an osmolality-dependent manner. Raffinose was also the most effective solute at increasing the proline incorporation. Furthermore, anti-TGF-beta antibody prevented the increase in proline incorporation induced by hypertonicity. These results suggest that hypertonicity promotes the processing of latent TGF-beta to the biologically active form, resulting in the stimulation of collagen synthesis in NRK cells.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Cell Line
  • Collagen / biosynthesis
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Hypertonic Solutions / pharmacology*
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism*
  • Proline / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Reference Values
  • Stress, Physiological / chemically induced
  • Stress, Physiological / metabolism*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism*


  • Antibodies
  • Hypertonic Solutions
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Collagen
  • Proline