کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8455339 | 1548021 | 2014 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A decorin-deficient matrix affects skin chondroitin/dermatan sulfate levels and keratinocyte function
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کلمات کلیدی
ECMEDSDCNFGFGAGSLRPdecorin - دکورینEhlers–Danlos syndrome - سندرم Ehlers-DanlosDermatan sulfate - سولفات درماتانfibroblast growth factor - فاکتور رشد فیبروبلاستExtracellular matrix - ماتریکس خارج سلولیsmall leucine-rich proteoglycan - پروتئگلیکان غنی از لوسین استChondroitin sulfate - کندرویتین سولفاتGlycosaminoglycan - گلیکوزآمینوگلیکان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Decorin is a small leucine-rich proteoglycan harboring a single glycosaminoglycan chain, which, in skin, is mainly composed of dermatan sulfate (DS). Mutant mice with targeted disruption of the decorin gene (Dcnâ/â) exhibit an abnormal collagen architecture in the dermis and reduced tensile strength, collectively leading to a skin fragility phenotype. Notably, Ehlers-Danlos patients with mutations in enzymes involved in the biosynthesis of DS display a similar phenotype, and recent studies indicate that DS is involved in growth factor binding and signaling. To determine the impact of the loss of DS-decorin in the dermis, we analyzed the glycosaminoglycan content of Dcnâ/â and wild-type mouse skin. The total amount of chondroitin/dermatan sulfate (CS/DS) was increased in the Dcnâ/â skin, but was overall less sulfated with a significant reduction in bisulfated ÎDiS2,X (XÂ =Â 4 or 6) disaccharide units, due to the reduced expression of uronyl 2-O sulfotransferase (Ust). With increasing age, sulfation declined; however, Dcnâ/â CS/DS was constantly undersulfated vis-Ã -vis wild-type. Functionally, we found altered fibroblast growth factor (Fgf)-7 and -2 binding due to changes in the micro-heterogeneity of skin Dcnâ/â CS/DS. To better delineate the role of decorin, we used a 3D Dcnâ/â fibroblast cell culture model. We found that the CS/DS extracts of wild-type and Dcnâ/â fibroblasts were similar to the skin sugars, and this correlated with the lack of uronyl 2-O sulfotransferase in the Dcnâ/â fibroblasts. Moreover, Ffg7 binding to total CS/DS was attenuated in the Dcnâ/â samples. Surprisingly, wild-type CS/DS significantly reduced the binding of Fgf7 to keratinocytes in a concentration dependent manner unlike the Dcnâ/â CS/DS that only affected the binding at higher concentrations. Although binding to cell-surfaces was quite similar at higher concentrations, keratinocyte proliferation was differentially affected. Higher concentration of Dcnâ/â CS/DS induced proliferation in contrast to wild-type CS/DS. 3D co-cultures of fibroblasts and keratinocytes showed that, unlike Dcnâ/â CS/DS, wild-type CS/DS promoted differentiation of keratinocytes. Collectively, our results provide novel mechanistic explanations for the reported defects in wound healing in Dcnâ/â mice and possibly Ehlers-Danlos patients. Moreover, the lack of decorin-derived DS and an altered CS/DS composition differentially influence keratinocyte behavior.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Matrix Biology - Volume 35, April 2014, Pages 91-102
Journal: Matrix Biology - Volume 35, April 2014, Pages 91-102
نویسندگان
Katerina Nikolovska, Jana K. Renke, Oliver Jungmann, Kay Grobe, Renato V. Iozzo, Alina D. Zamfir, Daniela G. Seidler,