Renin receptor expression in human adipose tissue
Renin receptor expression in human adipose tissue
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DOI：
10.1152/ajpregu.00439.2005
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发表时间：
2007-01-01
影响因子：
2.8
通讯作者：
Grino, Michel
中科院分区：
文献类型：
--
作者：
Achard, Vincent;Boullu-Ciocca, Sandrine;Grino, Michel
脂肪组织合成肾素-血管紧张素系统的所有成分。肾素受体（RenR）在与肾素结合时，能够提高其从血管紧张素原生成血管紧张素I的效率。我们证明，在分离的脂肪间基质细胞和基质区域中，RenR在人脂肪组织的基质部分特异性合成。RenR在细胞外周表达，强烈提示膜定位。在人间质细胞原代培养中，RenR蛋白的表达在分化过程中显著降低，而RenR mRNA的表达水平没有变化，表明RenR在前脂肪细胞和非前脂肪细胞中均有表达，并在转录后水平受到调控。人脂肪组织切片的双标记免疫组织化学显示，RenR与肾素共定位，而3T3-L1（一种前脂肪细胞系）与肾素孵化能刺激细胞内信号通路ERK 1/2的磷酸化状态，并且在原代培养的人脂肪基质细胞短时间暴露于肾素后，血管紧张素I生成的长期剂量依赖性增加，表明脂肪RenR是功能性的。通过大量人体脂肪组织活检，我们发现，与瘦肉和肥胖患者的皮下脂肪组织相比，内脏脂肪组织中RenR的表达增加。结合我们发现RenR与内脏脂肪组织纤维蛋白溶解系统的主要抑制剂型纤溶酶原激活物抑制剂1共定位，上述数据提示RenR在肥胖诱导的内脏脂肪组织积累及其伴随的心血管并发症中起作用。
Adipose tissue synthesizes all components of the renin-angiotensin system. The renin receptor (RenR) is able, on renin binding, to increase its efficiency to generate angiotensin I from angiotensinogen. We demonstrate that RenR is specifically synthesized in the stromal portion of human adipose tissue in both isolated interadipocyte stromal cells and in stromal areas. RenR is expressed at the periphery of cells, strongly suggesting a membranal localization. RenR protein expression in primary cultures of human stromal cells decreased significantly during differentiation, whereas RenR mRNA levels did not change, demonstrating that RenR was expressed in both preadipocyte and nonpreadipocyte cells, and was regulated at a posttranscriptional level. Double-labeling immunohistochemistry of human adipose tissue sections revealed that RenR was colocalized with renin, whereas incubation of 3T3-L1, a preadipocyte cell line, with renin stimulated the phosphorylation state of the intracellular signaling pathway ERK 1/2, and short exposure of human adipose stromal cells in primary culture to renin was followed by a long-lasting dose-dependent increase of angiotensin I generation, indicating that adipose RenR is functional. We show, using a large set of human adipose tissue biopsies, that RenR expression was increased in visceral compared with subcutaneous adipose tissue of lean and obese patients. Taken together with our finding that RenR was colocalized with plasminogen activator inhibitor type 1, the main inhibitor of the fibrinolytic system in visceral adipose tissue, the above-mentioned data suggest that RenR plays a role in obesity-induced visceral adipose tissue accumulation and its accompanying cardiovascular complications.