Deficiency of the decorin core protein in the variant form of Ehlers-Danlos syndrome with chronic skin ulcer.
Decorin belongs to a family of small leucine-rich dermatan sulfate proteoglycans that are involved in the control of matrix organization and cell growth. Here, we described a patient whose skin glycosaminoglycans showed extremely decreased amount of dermatan sulfate compared with a normal control skin. This patient presented clinical features of Ehlers-Danlos syndrome with a chronic skin ulcer. Western blotting revealed that the deficiency of dermatan sulfate was due to the defect of decorin core protein. Beta-xyloside, an initiator of dermatan sulfate glycosaminoglycan chain elongation, enhanced the synthesis of dermatan sulfate in the fibroblasts of the patient to a similar extent to that of control. This result indicated that the enzymes for the elogation of dermatan sulfate side chains were normal. Northern blotting demonstrated remarkable reduction of decorin mRNA level, while biglycan mRNA level was concomitantly increased and procollagen alpha1(I) mRNA level was normal. cDNA and exons sequencing analysis showed there was no mutation in decorin gene of the patient. IL-1beta stimulated decorin expression to about 140% in control fibroblasts while about 110% in patient fibroblasts. On the other hand, TGF-beta1 resulted in 40% reductions of decorin expression in both control and patient fibroblasts. These data suggested that reduced decorin expression of fibroblasts from the patient of Ehlers-Danlos syndrome may be due to abnormalities in the regulatory regions, which is responsible for the IL-1beta stimulation.
Wu
J
J
Department of Dermatology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. jinghaiwu@hotmail.com
Utani
A
A
Endo
H
H
Shinkai
H
H
D044466:Asian People; D002908:Chronic Disease; D058575:Decorin; D004535:Ehlers-Danlos Syndrome / Q000235:genetics*; D016326:Extracellular Matrix Proteins; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D014644:Genetic Variation; D006025:Glycosaminoglycans / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007564:Japan; D008408:Mastectomy / Q000009:adverse effects; D008875:Middle Aged; D011183:Postoperative Complications; D011509:Proteoglycans / Q000172:deficiency* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012883:Skin Ulcer / Q000209:etiology / Q000235:genetics*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D007375:Interleukin-1; D011509:Proteoglycans; D016212:Transforming Growth Factor beta