Additionally, heparanase augments the expression of TLRs in tubular epithelial cells, vascular endothelial cells, and infiltrating leukocytes during renal IRI, thus creating a positive pro-inflammatory feed-back which eventually leads to tubular cell apoptosis, immune activation, graft rejection and eventually chronic allograft nephropathy [111]. The gene discussed is HPSE; the disease is Crouzon syndrome-acanthosis nigricans syndrome.