Heparanase interacts with resistin and augments its activity

Area of Science:

• Biochemistry and Molecular Biology
• Cellular and Molecular Physiology
• Immunology

Background:

• Heparanase is a protein with known enzymatic and postulated non-enzymatic functions.
• A specific receptor mediating heparanase's non-enzymatic roles was hypothesized but not identified.
• Resistin is a protein implicated in inflammatory processes.

Purpose of the Study:

• To identify a potential receptor for heparanase involved in its non-enzymatic functions.
• To investigate the interaction between heparanase and other proteins.
• To elucidate the functional consequences of the heparanase-resistin interaction.

Main Methods:

• Affinity chromatography using immobilized heparanase on proteins from human urine.
• Co-immunoprecipitation assays to confirm protein-protein interactions.
• Enzyme-linked immunosorbent assay (ELISA) to quantify protein binding.
• Standard bioassay using THP1 cells to assess resistin bioactivity.

Main Results:

• Resistin was identified as a heparanase binding protein via affinity chromatography.
• Co-immunoprecipitation and ELISA confirmed the direct interaction between heparanase and resistin.
• Heparanase was found to potentiate the bioactivity of resistin in a monocytic cell differentiation assay.

Conclusions:

• Resistin acts as a binding protein for heparanase, potentially serving as its receptor.
• The heparanase-resistin complex enhances resistin's bioactivity, promoting THP1 cell differentiation into foam cells.
• This newly identified complex may play a significant role in inflammatory conditions influenced by both proteins.