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STEAP4是一种在脂肪组织中高表达的肿瘤坏死因子-α诱导基因,其下调与人类肥胖有关。

Downregulation of STEAP4, a highly-expressed TNF-alpha-inducible gene in adipose tissue, is associated with obesity in humans.

作者信息

Zhang Chun-Mei, Chi Xia, Wang Bin, Zhang Min, Ni Yu-Hui, Chen Rong-Hua, Li Xiao-Nan, Guo Xi-Rong

机构信息

Department of Pediatrics, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China.

出版信息

Acta Pharmacol Sin. 2008 May;29(5):587-92. doi: 10.1111/j.1745-7254.2008.00793.x.

Abstract

AIM

To determine the relationship between six-transmembrane epithelial antigen of the prostate 4 (STEAP4) expression and obesity.

METHODS

RT-PCR and immunoblot analyses were performed to determine the differential expressions of STEAP4 mRNA and protein, respectively, in human omental adipose tissue from obese patients and normal weight controls. The expression pattern of STEAP4 mRNA in various human tissues was determined by RT-PCR. The subcellular localization of the STEAP4 protein in human adipose tissue was confirmed by immunohistochemistry. Finally, we confirmed that cultured human omental adipose tissue undergoes TNF-alpha-mediated regulation of the STEAP4 expression.

RESULTS

STEAP4 mRNA and protein levels were downregulated in omental adipose tissue from obese patients relative to normal controls. The STEAP4 expression was most abundant in human adipose tissue. An immunohistochemical analysis confirmed that STEAP4 was associated with the plasma membrane of adipocytes. The STEAP4 expression was induced by TNF-alpha in a dose-dependent manner in human adipose tissue.

CONCLUSION

STEAP4 was abundantly expressed in human adipose tissue, and the STEAP4 expression was significantly downregulated in obese patients. STEAP4 localized to the plasma membrane of adipocytes, and the STEAP4 expression was induced by TNF-alpha in adipose tissue. These data suggest that STEAP4 may play a significant role in the development of human obesity.

摘要

目的

确定前列腺六跨膜上皮抗原4(STEAP4)表达与肥胖之间的关系。

方法

分别采用逆转录聚合酶链反应(RT-PCR)和免疫印迹分析,以确定肥胖患者和正常体重对照者的人网膜脂肪组织中STEAP4 mRNA和蛋白的差异表达。通过RT-PCR确定STEAP4 mRNA在各种人体组织中的表达模式。通过免疫组织化学证实STEAP4蛋白在人脂肪组织中的亚细胞定位。最后,我们证实培养的人网膜脂肪组织经历肿瘤坏死因子-α(TNF-α)介导的STEAP4表达调控。

结果

与正常对照相比,肥胖患者网膜脂肪组织中STEAP4 mRNA和蛋白水平下调。STEAP4在人脂肪组织中表达最为丰富。免疫组织化学分析证实STEAP4与脂肪细胞膜相关。在人脂肪组织中,TNF-α以剂量依赖方式诱导STEAP4表达。

结论

STEAP4在人脂肪组织中大量表达,且肥胖患者中STEAP4表达明显下调。STEAP4定位于脂肪细胞膜,且在脂肪组织中TNF-α可诱导STEAP4表达。这些数据表明STEAP4可能在人类肥胖的发生发展中起重要作用。

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