کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2121257 1085773 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Soluble CLEC2 Extracellular Domain Improves Glucose and Lipid Homeostasis by Regulating Liver Kupffer Cell Polarization
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Soluble CLEC2 Extracellular Domain Improves Glucose and Lipid Homeostasis by Regulating Liver Kupffer Cell Polarization
چکیده انگلیسی


• CLEC2, a type II C-type lectin-like receptor, is expressed on a variety of cell types including Kupffer cells.
• Overexpression of CLEC2 ECD in mice improves glucose and lipid parameters and induces markers of alternatively activated Kupffer cells.
• CLEC2 is a promising therapeutic target for the treatment of diabetes and liver diseases.

The polarization of tissue resident macrophages toward the alternatively activated, anti-inflammatory M2 phenotype is believed to positively impact obesity and insulin resistance. Here we show that the soluble form of the extracellular domain (ECD) of C-type lectin-like receptor 2, CLEC2, regulates Kupffer cell polarization in the liver and improves glucose and lipid parameters in diabetic animal models. Over-expression of Fc-CLEC2(ECD) in mice via in vivo gene delivery, or injection of recombinant Fc-CLEC2(ECD) protein, results in a reduction of blood glucose and liver triglyceride levels and improves glucose tolerance. Furthermore, Fc-CLEC2(ECD) treatment improves cytokine profiles and increases both the M2 macrophage population and the genes involved in the oxidation of lipid metabolism in the liver. These data reveal a previously unidentified role for CLEC2 as a regulator of macrophage polarity, and establish CLEC2 as a promising therapeutic target for treatment of diabetes and liver disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: EBioMedicine - Volume 2, Issue 3, March 2015, Pages 214–224
نویسندگان
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