Histories of Dermatan Sulfate Epimerase and Dermatan 4- O -Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome.
Shuji MizumotoShuhei YamadaPublished in: Genes (2023)
Dermatan sulfate (DS) and its proteoglycans are essential for the assembly of the extracellular matrix and cell signaling. Various transporters and biosynthetic enzymes for nucleotide sugars, glycosyltransferases, epimerase, and sulfotransferases, are involved in the biosynthesis of DS. Among these enzymes, dermatan sulfate epimerase (DSE) and dermatan 4- O -sulfotranserase (D4ST) are rate-limiting factors of DS biosynthesis. Pathogenic variants in human genes encoding DSE and D4ST cause the musculocontractural type of Ehlers-Danlos syndrome, characterized by tissue fragility, joint hypermobility, and skin hyperextensibility. DS-deficient mice exhibit perinatal lethality, myopathy-related phenotypes, thoracic kyphosis, vascular abnormalities, and skin fragility. These findings indicate that DS is essential for tissue development as well as homeostasis. This review focuses on the histories of DSE as well as D4ST, and their knockout mice as well as human congenital disorders.
Keyphrases
- extracellular matrix
- endothelial cells
- induced pluripotent stem cells
- genome wide
- pluripotent stem cells
- soft tissue
- small molecule
- spinal cord
- pregnant women
- wound healing
- mesenchymal stem cells
- copy number
- single cell
- cell therapy
- gene expression
- genome wide identification
- cell wall
- spinal cord injury
- dna methylation
- transcription factor
- genome wide analysis
- myasthenia gravis