Excess glucose induce trophoblast inflammation and limit cell migration through HMGB1 activation of Toll‐Like receptor 4

Abstract

The findings from this study indicate a novel mechanism by which hyperglycemia may impact trophoblast function, early placentation, and ultimately, pregnancy outcome.

Modulation of trophoblast function by concurrent hyperglycemia and antiphospholipid antibodies is in part TLR4‐dependent

“…27,30,31 In parallel, we also demonstrated inhibition of spontaneous trophoblast migration in the presence of excess glucose or aPL. Since we had identified a role for TLR4 in mediating some trophoblast responses to aPL and excess glucose, [27][28][29][30] this study also aimed to investigate the potential role of TLR4 in trophoblast responses to concurrent aPL and hyperglycemic conditions. Since we had identified a role for TLR4 in mediating some trophoblast responses to aPL and excess glucose, [27][28][29][30] this study also aimed to investigate the potential role of TLR4 in trophoblast responses to concurrent aPL and hyperglycemic conditions.…”

“…30 Similarly, the 10.5 ± 5.2% further reduction in cell migration under independently increase the risk of a woman developing preeclampsia. 30 Similarly, the 10.5 ± 5.2% further reduction in cell migration under independently increase the risk of a woman developing preeclampsia.…”

“…44 Specifically, TLR4 activation of the placental trophoblasts by danger signals leading to an inflammatory response has been linked to preeclampsia. 30 However, the underlying mechanism of how concurrent diabetes and aPL may lead to preeclampsia is not fully understood. 30 However, the underlying mechanism of how concurrent diabetes and aPL may lead to preeclampsia is not fully understood.…”

“…[27][28][29][30] Additionally, we showed that in a TLR4independent manner, excess glucose and aPL independently altered production of anti-angiogenic soluble endoglin (sEndoglin), and soluble fms-like tyrosine kinase 1 (sFlt-1), as well as pro-angiogenic placental growth factor (PlGF). [27][28][29][30] Additionally, we showed that in a TLR4independent manner, excess glucose and aPL independently altered production of anti-angiogenic soluble endoglin (sEndoglin), and soluble fms-like tyrosine kinase 1 (sFlt-1), as well as pro-angiogenic placental growth factor (PlGF).…”

“…[27][28][29][30] Additionally, we showed that in a TLR4independent manner, excess glucose and aPL independently altered production of anti-angiogenic soluble endoglin (sEndoglin), and soluble fms-like tyrosine kinase 1 (sFlt-1), as well as pro-angiogenic placental growth factor (PlGF). 27,30 Therefore, the objective of this study was, using our in vitro models, to assess the effects of combination of excess glucose and low-dose aPL on trophoblast function by measuring trophoblast production of inflammatory and angiogenic factors, and cell migration. 27,30 Therefore, the objective of this study was, using our in vitro models, to assess the effects of combination of excess glucose and low-dose aPL on trophoblast function by measuring trophoblast production of inflammatory and angiogenic factors, and cell migration.…”