Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Myofibroblastic differentiation leads to hyaluronan accumulation through reduced hyaluronan turnover

Jenkins, Robert Hywel, Thomas, Gareth John, Williams, John David and Steadman, Robert 2004. Myofibroblastic differentiation leads to hyaluronan accumulation through reduced hyaluronan turnover. The Journal of Biological Chemistry 279 (40) , pp. 41453-41460. 10.1074/jbc.M401678200

Full text not available from this repository.


During the initiation and progression of fibrosis there is extensive differentiation of cells to a myofibroblastic phenotype. Because the synthesis of hyaluronan (HA) was recently linked to oncogenic epithelial-mesenchymal transformation, the present study investigated whether increased HA synthesis was also associated with myofibroblastic differentiation. HA synthesis and size were measured by incorporation of [(3)H]glucosamine, ion exchange, and size exclusion chromatography. Hyaluronan synthase (HAS) or hyaluronidase (HYAL) mRNA levels were assessed by reverse transcription-PCR. HYAL was detected by immunoblotting and the degradation of [(3)H]HA. Between 2- and 3-fold more HA appeared in the conditioned medium and became associated with the cells upon myofibroblastic differentiation. Inhibition of HAS and examination of HAS mRNA expression demonstrated that this was not the result of increased synthesis of HA or the induction of HAS 2. After differentiation, however, myofibroblasts metabolized exogenously supplied [(3)H]HA at a slower rate than fibroblasts and expressed lower levels of both HYAL 1 and HYAL 2 mRNA. Immunoblotting revealed more HYAL 1 and 2 in the myofibroblast conditioned medium. After acidification, however, there was no difference in HA degradation. This suggests that much of the released HYAL is inactive and that the observed differences in HA degradation are caused by cell-associated rather than secreted activity. This was confirmed by immunohistochemical staining for HYAL 1 and HYAL 2. This finding indicates the potential importance of the HYAL enzymes in controlling fibrotic progression and contrasts HA synthesis as a mediator of oncogenic transformation with that of HA degradation controlling fibrogenic differentiation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 1083-351X
Last Modified: 30 Jun 2017 01:31

Citation Data

Cited 54 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item