Effects of mannose-6-phosphate on human fibroblast cells - biomed 2010

Coordinate expression of CTGF and TGF-ss plays an important role in tissue fibrosis. Expression of these factors is increased under hypoxic conditions. Treatment of cells under hypoxic conditions with fructose-1,6-bisphosphate has been previously shown to decrease production of CTGF [1]. Mannose-6-phosphate (M6P) may function to down regulate fibrosis by bypassing substrate-level phosphorylation in glycolysis or through competitive inhibition of activation of TGF-ss at the M6P/IGFII receptor. Human fibroblast cells were treated for 24, 48, or 72 hours with 0.5 M, 5 M, and 50 M concentrations of M6P. Cell counts, MDA assay, and cell staining were performed after treatment. At 24 hours cell counts for low and medium treatment groups were higher than the control group, but this difference was significant for only the low group. This effect was not seen at 48 or 72 hours. Cell counts for all treatment and control groups dropped significantly after 24 hours. MDA assay showed reduction in cellular damage with low and medium doses of M6P, but with high dose M6P cellular damage approximates that of controls. Additional studies are needed to determine whether M6P dcreases production of CTGF and/or TGF-ss. David A. Black, Alex Whittington, Tamika Taylor, Olga Golanov, Michelle Tucci, and Hamed Benghuzzi.