Selective enhancement by cyclosporin A of collagen expression by mesangial cells 'in culture'

Gian Marco Ghiggeri, Paola Altieri, Roberta Oleggini, Franca Spada, Fabrizio Ginevri, Francesco Perfumo, Rosanna Gusmano

Research output: Contribution to journalArticlepeer-review

Abstract

Extracellular matrix deposition in mesangial areas leading to glomerulosclerosis is the major side effect of protracted therapies with cyclosporin A. In order to define any direct correlation between a chronic therapy with the drug and glomerulosclerosis we studied the effects of cyclosporin A on extracellular matrix production by human mesangial cells in culture. By immunoprecipitation and sodium dodecyl sulfate polyacrylamide electrophoresis (SDS-PAGE) of [3H]proline-labeled mesangial cells it was found that cyclosporin A induced a dose-dependent increase in total collagen synthesis (+80%), corresponding to a net increment in collagen III (+120%) and in a component with 70 kDa molecular weight which was produced only in negligible amount by mesangial cells under standard conditions. This collagen was characterized by cyanogen bromide digestion and finger print analysis as a novel molecule, not sharing any peptide composition similarities with the already characterized collagens. These data indicate that cyclosporin A stimulates the synthesis by mesangial cells of selected collagens, mainly collagen III and a new low molecular weight component. This mechanism may be relevant in cyclosporin A induced glomerulosclerosis occuring during protracted therapies with the drug.

Original languageEnglish
Pages (from-to)195-201
Number of pages7
JournalEuropean Journal of Pharmacology: Environmental Toxicology and
Volume270
Issue number2-3
DOIs
Publication statusPublished - Apr 4 1994

Keywords

  • Cyclosporin A
  • Extracellular matrix
  • Glomerulosclerosis
  • Mesangial cell

ASJC Scopus subject areas

  • Pollution
  • Pharmacology
  • Toxicology

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