期刊
FEBS JOURNAL
卷 280, 期 10, 页码 2431-2446出版社
WILEY
DOI: 10.1111/febs.12214
关键词
cancer; dermatan sulfate epimerase; DSE; DSEL; iduronic acid; inflammation; proteoglycans
资金
- Swedish Science Research Council
- Medical Faculty of Lund University
- Mizutani Foundation for Glycoscience
- Albert Osterlund Foundation
- Greta and Johan Kock Foundation
- Anna-Greta Crafoord Foundation
The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of EhlerDanlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease.
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