Other reported molecules affecting HMGB-1 signaling that could be of some interest for SSc are thrombomodulin, haptoglobin, metformin, and glycyrrhizin, a natural triterpene glycoside investigated in several HMGB1-related diseases, proving to inhibit extracellular HMGB1 cytokine activity and protect against ischemia/reperfusion (I/R)-induced injury in animal models. This evidence concerns the gene HP and systemic sclerosis.