Soluble CLEC2 Extracellular Domain Improves Glucose and Lipid Homeostasis by Regulating Liver Kupffer Cell Polarization.
Soluble CLEC2 Extracellular Domain Improves Glucose and Lipid Homeostasis by Regulating Liver Kupffer Cell Polarization.
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DOI：
10.1016/j.ebiom.2015.02.013
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发表时间：
2015-03
期刊：
影响因子：
11.1
通讯作者：
Li, Yang
中科院分区：
文献类型：
--
作者：
Wu, Xinle;Zhang, Jun;Ge, Hongfei;Gupte, Jamila;Baribault, Helene;Lee, Ki Jeong;Lemon, Bryan;Coberly, Suzanne;Gong, Yan;Pan, Zheng;Rulifson, Ingrid C.;Gardner, Jonitha;Richards, William G.;Li, Yang
认为组织驻留巨噬细胞朝向交替活化的抗炎M2表型的极化对肥胖和胰岛素抵抗有积极影响。在这里，我们表明，可溶性形式的胞外区（ECD）的C型凝集素样受体2，CLEC 2，调节库普弗细胞在肝脏中的极化，并改善糖尿病动物模型中的血糖和血脂参数。通过体内基因递送或注射重组Fc-CLEC 2（ECD）蛋白在小鼠中过表达Fc-CLEC 2（ECD）导致血糖和肝脏甘油三酯水平降低并改善葡萄糖耐量。此外，Fc-CLEC 2（ECD）治疗改善了细胞因子谱，并增加了M2巨噬细胞群和参与肝脏脂质代谢氧化的基因。这些数据揭示了CLEC 2作为巨噬细胞极性调节剂的先前未鉴定的作用，并确立了CLEC 2作为治疗糖尿病和肝病的有希望的治疗靶点。CLEC 2是一种II型C型凝集素样受体，在包括枯否细胞在内的多种细胞类型上表达。CLEC 2 ECD在小鼠中的过表达改善了葡萄糖和脂质参数，并诱导了交替激活的枯否细胞的标志物。CLEC 2是治疗糖尿病和肝脏疾病的有前景的治疗靶点。
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. 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.
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DOI：
10.1042/bj20071216
发表时间：
2008-04-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Christou CM;Pearce AC;Watson AA;Mistry AR;Pollitt AY;Fenton-May AE;Johnson LA;Jackson DG;Watson SP;O'Callaghan CA
通讯作者：
O'Callaghan CA
DOI：
10.4049/jimmunol.0802808
发表时间：
2009-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kerrigan AM;Dennehy KM;Mourão-Sá D;Faro-Trindade I;Willment JA;Taylor PR;Eble JA;Reis e Sousa C;Brown GD
通讯作者：
Brown GD
影响因子：
7.7
作者：
Lumeng, Carey N.;DeYoung, Stephanie M.;Saltiel, Alan R.
通讯作者：
Saltiel, Alan R.
DOI：
10.1152/ajpgi.00391.2009
发表时间：
2010-01-01
影响因子：
4.5
作者：
Lanthier, Nicolas;Molendi-Coste, Olivier;Leclercq, Isabelle A.
通讯作者：
Leclercq, Isabelle A.
影响因子：
3
作者：
Plotkin, BJ;Paulson, D;Casteel, N
通讯作者：
Casteel, N