Apoptosis induced by serum withdrawal in human mesangial cells. Role of IGFBP-3.
Apoptosis has been reported to occur both during the course of kidney development and the progression of kidney injury to scarring. Insulin-like growth factor binding protein-3 (IGFBP-3), a component of the IGF system, has been shown to induce apoptosis in cancer cell lines. However, if IGFBP-3 has similar effects in human mesangial cells (HMC) remains unknown. The purpose of this study was to examine the expression of IGFBP-3 and its possible effect on the induction of apoptosis in HMC during serum deprivation. We have observed that IGFBP-3 accumulates progressively in HMC in which serum has been withdrawn. In these cells, an increase of IGFBP-3 is observed before the production of apoptosis suggesting a link between these phenomena. Furthermore, the addition of IGFBP-3 in physiological amounts (from 100 to 400 ng/ml) to culture medium devoid of growth factors accelerates and increases the apoptotic process with a dose-dependent effect. These findings suggest that IGFBP-3 is a mediator of cell death in human mesangial cells when the availability of growth factors is curtailed. These data also suggest that IGFBP-3 could contribute to apoptotic processes observed in human disease.
Verzola
D
D
Division of Nephrology, Department of Internal Medicine, Genoa, Italy.
Villaggio
B
B
Berruti
V
V
Gandolfo
M T
MT
Deferrari
G
G
Garibotto
G
G
D017209:Apoptosis / Q000502:physiology*; D001790:Blood Physiological Phenomena; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D018972:Insulin-Like Growth Factor Binding Protein 3