Hyaluronan histochemistry - A potential new tool to assess the progress of liver disease from simple steatosis to hepatocellular carcinoma
Files
Self archived version
final draftDate
2019Author(s)
Unique identifier
10.1093/glycob/cwz002Metadata
Show full item recordMore information
Self-archived item
Citation
Mustonen, Anne-Mari. Salvén, Anu. Kärjä, Vesa. Rilla, Kirsi. Matilainen, Johanna. Nieminen, Petteri. (2019). Hyaluronan histochemistry - A potential new tool to assess the progress of liver disease from simple steatosis to hepatocellular carcinoma. Glycobiology, 29 (4) , 298-306. 10.1093/glycob/cwz002.Rights
Abstract
Nonalcoholic fatty liver disease is among the most common liver diseases worldwide and one cause of cirrhosis that can result in the development of hepatocellular carcinoma (HCC). Hyaluronan (HA) is a high-molecular-mass glycosaminoglycan with diverse functions in tissue injury and repair, for instance, in inflammation and fibrogenesis. The aim of the present study was to investigate the relationships between the HA synthesizing and degrading enzymes in a spectrum of liver pathologies. This was realized by histological staining of liver sections from controls and patients with simple steatosis, steatohepatitis, cirrhosis and HCC (n = 90). HA-positive staining intensified in connective tissue in all liver pathologies, and staining of CD44, the major HA receptor, similarly increased in steatohepatitis and cirrhosis. HA synthase 1 (HAS1)-positive staining was reduced in steatosis, steatohepatitis and HCC. Staining of HAS3, which produces HA of a lower molecular mass, promotes inflammation and is pathogenic in animal models, increased in all diagnoses. The responses in staining intensity of HAS2 and hyaluronidases 1–2 were specific for different cell types. These findings suggest that HAS1–2 are responsible for HA synthesis in healthy livers, while HAS3 increases in importance in liver diseases. It is noteworthy that the pathological changes in HA metabolism are already visible in simple steatosis and, thus, precede the histological changes of inflammation and fibrosis. It could be possible to intervene in disease progression at an early stage by influencing HA metabolism. The results could have potential clinical applications with HAS3 immunostaining supplementing the existing HCC diagnostics.
Keywords
Link to the original item
http://dx.doi.org/10.1093/glycob/cwz002Publisher
Oxford University Press (OUP)Collections
- Terveystieteiden tiedekunta [1789]