Hyaluronan accumulates with high-fat feeding and contributes to insulin resistance.

Increased deposition of specific extracellular matrix (ECM) components is a characteristic of insulin-resistant skeletal muscle. Hyaluronan (HA) is a major constituent of the ECM. The hypotheses that 1) HA content is increased in the ECM of insulin-resistant skeletal muscle and 2) reduction of HA in the muscle ECM by long-acting pegylated human recombinant PH20 hyaluronidase (PEGPH20) reverses high-fat (HF) diet-induced muscle insulin resistance were tested.

Mutations in the catalytic domain of human matrix metalloproteinase-1 (MMP-1) that allow for regulated activity through the use of Ca2+.

Conditionally active proteins regulated by a physiological parameter represent a potential new class of protein therapeutics. By systematically creating point mutations in the catalytic and linker domains of human MMP-1, we generated a protein library amenable to physiological parameter-based screening. Mutants screened for temperature-sensitive activity had mutations clustered at or near amino acids critical for metal binding.

A comprehensive model of hyaluronan turnover in the mouse.

The metabolism of hyaluronan (HA), especially its catabolism, is still far from being elucidated. Although several studies suggest that HA is degraded locally in tissues and through the lymphatic or circulatory systems, much needs to be learned about the enzymes, receptors and cell types that support this dynamic process. In the current work, the clearance of exogenously administered HA was examined in a C57BL/6 mouse model.

Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models.

Hyaluronan (HA) is a glycosaminoglycan polymer that often accumulates in malignancy. Megadalton complexes of HA with proteoglycans create a hydrated connective tissue matrix, which may play an important role in tumor stroma formation. Through its colloid osmotic effects, HA complexes contribute to tumor interstitial fluid pressure, limiting the effect of therapeutic molecules on malignant cells.