Sulfatide inhibits fibroblast growth, activation and oxidative stress induced by ectopic insulin.

AIM

To study the effect of sulfatide on gene expression and proliferation of human primary fibroblasts induced by insulin, insulin-like growth factor-1 and human growth hormone.

MATERIALS AND METHODS

Human primary fibroblasts were exposed to 1, 3 and 30 μM of sulfatide or its precursor galactosylceramide (GalCer). Proliferation was determined by H-thymidine incorporation and gene expression via microarray analysis.

RESULTS

Sulfatide and GalCer reduced the growth rate of fibroblasts by 32%-82% when exposed to 0.5 nM insulin. After challenge with 120 μM of H O , sulfatide reduced membrane leakage. Fibroblast gene expression was altered by sulfatide in gene pathways associated with cell cycle/growth, transforming growth factor-β function, and encoding of proteins involved in intracellular signalling. NFKBIA, a key control element in NF-кB regulation, was decreased 2-fold by sulfatide.

CONCLUSIONS

Sulfatide strongly inhibits fibroblast growth. We therefore suggest the addition of sulfatide to injectable commercial insulin formulations, which would reduce adverse fibroblast growth and improve well-being in patients with diabetes.