CCN5/WISP2 and metabolic diseases.
CCN5/WISP2 and metabolic diseases.
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DOI：
10.1007/s12079-017-0437-z
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发表时间：
2018-03
影响因子：
4.1
通讯作者：
Smith U
中科院分区：
文献类型：
--
作者：
Grünberg JR;Elvin J;Paul A;Hedjazifar S;Hammarstedt A;Smith U
肥胖和2型糖尿病在世界范围内以流行病的速度增加。预计到2030年，约有5亿人将患有糖尿病;主要是2型糖尿病。CCN蛋白家族由于其对间充质干细胞（MSC）增殖和分化的影响以及作为纤维化的重要调节剂而在代谢和其他常见人类疾病中变得令人感兴趣。我们在这里审查目前的知识WNT 1诱导信号通路蛋白2（CCN 5/WISP 2）。它已被证明是通过对经典WNT和TGFβ途径的影响而对这两个过程起重要调节作用。与传统的经典WNT配体相比，它也在成脂定向因子BMP 4的正常调节下，并允许MSC经历正常的脂肪细胞分化。CCN 5/WISP 2在MSC中高度表达并由MSC分泌，并且是MSC生长的重要调节剂。在脂肪组织中过表达CCN 5/WISP 2的转基因小鼠模型中，我们已经表明它在血液中分泌和循环，小鼠产生细胞过多的白色和棕色脂肪组织，具有增加的瘦体重和增大的细胞过多的心脏。肥胖的转基因小鼠具有改善的胰岛素敏感性。有趣的是，CCN 5/WISP 2的抗纤维化作用通过抑制TGFβ通路而保护免于心力衰竭。了解CCN 5/WISP 2如何调节和信号是重要的，可能有助于开发肥胖和代谢疾病的新治疗策略，也可以成为再生医学的目标。
Obesity and type 2 diabetes increase worldwide at an epidemic rate. It is expected that by the year 2030 around 500 million people will have diabetes; predominantly type 2 diabetes. The CCN family of proteins has become of interest in both metabolic and other common human diseases because of their effects on mesenchymal stem cell (MSCs) proliferation and differentiation as well as being important regulators of fibrosis. We here review current knowledge of the WNT1 inducible signaling pathway protein 2 (CCN5/WISP2). It has been shown to be an important regulator of both these processes through effects on both the canonical WNT and the TGFβ pathways. It is also under normal regulation by the adipogenic commitment factor BMP4, in contrast to conventional canonical WNT ligands, and allows MSCs to undergo normal adipose cell differentiation. CCN5/WISP2 is highly expressed in, and secreted by, MSCs and is an important regulator of MSCs growth. In a transgenic mouse model overexpressing CCN5/WISP2 in the adipose tissue, we have shown that it is secreted and circulating in the blood, the mice develop hypercellular white and brown adipose tissue, have increased lean body mass and enlarged hypercellular hearts. Obese transgenic mice had improved insulin sensitivity. Interestingly, the anti-fibrotic effect of CCN5/WISP2 is protective against heart failure by inhibition of the TGFβ pathway. Understanding how CCN5/WISP2 is regulated and signals is important and may be useful for developing new treatment strategies in obesity and metabolic diseases and it can also be a target in regenerative medicine.
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影响因子：
4.1
作者：
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通讯作者：
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影响因子：
4.8
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通讯作者：
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影响因子：
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通讯作者：
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