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 ³ 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 H₂ O₂ , 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.