Our results showed that inhibiting the HMGB1 and TLR4/MyD88 signaling pathway alleviated glycocalyx shedding and GEC injury in MRL/lpr mice and LN plasma-stimulated HRGECs, which will provide a new direction for therapeutic target of endothelial injury and proteinuria in LN. This evidence concerns the gene TLR4 and lobular neoplasia.