کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5649793 | 1407131 | 2017 | 30 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ganglioside GM3 Mediates Glucose-Induced Suppression of IGF-1 Receptor-Rac1 Activation to Inhibit Keratinocyte Motility
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کلمات کلیدی
shRNAGCSINHEKGCsSNAIGF1RIGF-1antisense oligonucleotide - oligonucleotide antisenseSmall interfering RNA - RNA تداخل کوچکshort hairpin RNA - RNA موی سر کوتاهsiRNA - siRNAinsulin-like growth factor-1 - انسولین مانند عامل رشد 1Glucosylceramide synthase inhibitor - مهار کننده سنتاز گلوکوزیلسرامیدNormal human epidermal keratinocyte - کراتینوسیت اپیدرمی طبیعی انسانglucosylceramide synthase - گلوکوزیلسرامید سنتازinsulin receptor - گیرنده انسولینInsulin-like growth factor-1 receptor - گیرنده فاکتور 1 رشد انسولین
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
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چکیده انگلیسی
Activation of insulin-like growth factor-1 (IGF-1) receptor (IGF1R) signaling induces keratinocyte migration, but little is known about its regulation, including in diabetic wounds. GM3, a lipid raft ganglioside synthesized by GM3 synthase (GM3S), regulates receptor signaling. In diabetic mice, knockout or topically applied nanoconstruct-mediated knockdown of GM3S promotes wound edge IGF1R phosphorylation and re-epithelialization. Through modulating GM3 expression, we explored the role of GM3 in regulating human keratinocyte IGF1R signaling. Increases in GM3 and GM3S expression, including by exposure to high glucose, inhibit keratinocyte migration and IGF-1-induced chemotaxis in association with inhibition of IGF1R phosphorylation, suppression of Rac1 signaling, and activation of RhoA signaling. In contrast, GM3 depletion accelerates cell migration; increases cell velocity, displacement, and persistence; and activates IGF1R-Rac1 signaling. These data implicate GM3 in mediating glucose-induced suppression of IGF1R-Rac1 signaling. Furthermore, our findings provide evidence of a pivotal role for GM3-induced insulin resistance in impairing keratinocyte migration and reinforce the previously published studies in diabetic mice supporting GM3-depleting strategies as an approach for accelerating the healing of human diabetic wounds.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 137, Issue 2, February 2017, Pages 440-448
Journal: Journal of Investigative Dermatology - Volume 137, Issue 2, February 2017, Pages 440-448
نویسندگان
Duncan Hieu M. Dam, Xiao-Qi Wang, Sarah Sheu, Mahima Vijay, Desmond Shipp, Luke Miller, Amy S. Paller,