TLR4 and Hyperglycemia: In keratinocytes, hyperglycemia dose-dependently up-regulates the expression of TNF-α to reduce the expression of Thrombomodulin (TM) and TLR4, exogenous supplementation of Recombinant sTM can increase the expression of TLR4 and promote DW healing (Cheng et al., 2015).