Autoimmune Diseases
Diabetes: Heparanase & suppression of Diabetic Nephropathy
The enzyme heparanase is responsible for release and activation of various growth-promoting molecules, and degradation of non-cellular components in tissue matrices. As a result, it plays a dominant role in the process of tissue regeneration, which is desired in various acute and chronic pathological conditions.
In the setting of wound healing, traumatic tissue disruption destroys the cellular elements of the tissue, but at the same time initiates the heparanase-mediated healing process. In the setting of tissue engraftment (e.g., organ transplantation), heparanase is responsible for releasing and activating pro-angiogenic molecules, which promote the formation of new blood vessels and their growth into the newly transplanted organ.
Diabetes: suppression of diabetic nephropathy
Nephropathy is one of the major life-threatening complications of diabetes mellitus. Elevated levels of heparanase are found in the kidneys and urine of patients with diabetic nephropathy (DN) and other kidney complications. We have generated a strain of genetically-engineered mice in which the gene for heparanase has been deleted (Hpa-KO knockout mice) and demonstrated that unlike their wild type littermates, diabetic Hpa-KO mice fail to develop proteinuria and kidney damage. Moreover, using mouse models of type 1 and type 2 diabetes mellitus, we obtained a marked inhibition of proteinuria in response to treatment with non-anticoaguant glycol-split heparin (a potent inhibitor of heparanase enzymatic activity). This finding lends support to the potential clinical use of heparanase in the treatment of diabetic nephropathy and related kidney complications.
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