Increased HAS2-driven hyaluronic acid synthesis in shar-pei dogs with hereditary cutaneous hyaluronosis (mucinosis).

ABSTRACT

The Chinese shar-pei dog is known for its distinctive feature of wrinkled and thickened skin, defined as primary or hereditary cutaneous mucinosis. In a recent report, we identified the mucinous material deposited in the shar-pei skin as the polysaccharide hyaluronan (HA). In the present work, the molecular and cellular mechanisms underlying this phenotype have been identified in dermal fibroblasts isolated from shar-pei dogs. The production of HA, which appeared to be mainly associated with cell membrane protrusions and also intracellular, was higher in shar-pei fibroblasts than in control cells. The HA accumulation is related to a higher mRNA expression of the isoform HAS2 of the HA-synthesizing enzyme family, hyaluronan synthases (HAS). The higher expression of HAS2 in shar-pei fibroblasts was confirmed at the protein level. The other HAS isoenzymes, HAS1 and HAS3, and the HA-degrading enzymes, Hyal1 and Hyal2, were not differentially expressed in shar-pei fibroblasts compared with cells from control dogs. Fibroblasts from shar-pei dogs and from control dogs are morphologically different as observed by transmission electron microscopy. Scanning electron microscopy revealed a large number of cellular protrusions with associated globular deposits. Electron microscopy after labelling with biotinylated HA-binding protein confirmed an increased HA content in shar-pei fibroblasts, which could be localized in several subcellular structures. The authors propose the name hereditary cutaneous hyaluronosis (HCH) for affected dogs, because it better defines the cutaneous mucinosis of shar-pei dogs.