Hyperglycemia Induces Altered Expressions of Angiogenesis Associated Molecules in the Trophoblast

Figure 8

The effect of hyperglycemia induced altered glycosylation on the expressions of proinflammatory and chemokines in 3A-Sub-E trophoblast cells. Real-time quantitative polymerase chain reaction (RT-PCR) was performed to quantitatively measure. (a) The mRNA level of the indicated genes in responses to high glucose culture condition was increased at least 2 folds except IL-8 expression in 3A-Sub-E cells. (b) The mRNA expressions of IL-6, IL-8, and MCP-1 (CCL2) in 3A-Sub-E cells, were exposed to 30 mM D-glucose (black bar) or to 5.6 mM of D-glucose (normal control, grey bar) for 24 h followed by GAG degradation enzyme treatment with heparanase III (HepIII), chondroitinase ABC (Chabc), or both. Significantly increased expressions of IL-6, IL-8, and MCP-1 were occurred while 3A-Sub-E cells with Chondroitinase ABC treatment. (c) A diagram describes hyperglycemia-induced alterations of GAG substitution on perlecan (shorter and more chondroitin sulfate (CS) substituted than heparan sulfate (HS)) and matrix degradation by decreased TIMP-2 and increased activities of MMP2 and MMP9 resulting in the release of IL-6, RANTES, and bFGF into the extracellular matrix (soluble form) and enhance deposition of IL-8 and MCP-1 on the cell surfaces. The altered extracellular environment and the cell-associated and the soluble cytokine may contribute to the expressions of the indicated cytokines and chondroitin sulfate proteoglycans such as decorin at transcriptional and translational levels.