Figure 2.
Protective effects of Hpa2 against cancer, inflammation, and tissue damage. Hpa2 functions in heparanase‐dependent and independent manners, and affects gene expression (i.e., Sox2, Id1, Lox), tumor vascularity, ER stress, and cell apoptosis, resulting in cancer suppression. 2 , 106 , 107 , 114 , 129 Hpa2 levels are elevated in response to stress conditions, generating a vicious cycle that contributes to attenuation of tumor progression. Hpa2 exerts a protective effect in models of sepsis, endotoxemia, diabetes‐induced renal inflammation, pancreatitis, and in patients with Covid‐19, attributed, in part, to inhibition of heparanase‐mediated damage to the integrity of the glycocalyx. 116 , 117 , 118 Covid‐19, coronavirus disease 2019; ER, endoplasmic reticulum; Hpa2, heparanase‐2.