Jeon Jun Ho, Kim Kun-yong, Kim Jae Hyeong, Baek Ahmi, Cho Hyungin, Lee Young Ho, Kim Jong Wan, Kim Dohee, Han Seung Hyun, Lim Jong-Seok, Kim Keun Il, Yoon Do Young, Kim Soo-Hyun, Oh Goo Taeg, Kim Eunjoon, Yang Young
Department of Life Science, Sookmyung Women's University, Seoul 140-742, Korea.
FASEB J. 2008 May;22(5):1502-11. doi: 10.1096/fj.07-9412com. Epub 2008 Jan 2.
Complement-C1q TNF-related protein 1 (CTRP1), a member of the CTRP superfamily, is expressed at high levels in adipose tissues of obese Zucker diabetic fatty (fa/fa) rats, and CTRP1 expression is induced by proinflammatory cytokines, including TNF-alpha and IL-1beta. In the present study, we investigated stimulation of aldosterone production by CTRP1, since it was observed that CTRP1 was specifically expressed in the zona glomerulosa of the adrenal cortex, where aldosterone is produced. Increased aldosterone production by CTRP1 in cells of the human adrenal cortical cell line H295R was dose-dependent. Expression levels of aldosterone synthase CYP11B2 were examined to investigate the molecular mechanisms by which CTRP1 enhances the production of aldosterone. The expression of CYP11B2 was greatly increased by treatment with CTRP1, as was the expression of the transcription factors NGFIB and NURR1, which play critical roles in stimulation of CYP11B2 gene expression. It was also revealed that angiotensin II-induced aldosterone production is, at least in part, mediated by the stimulation of CTRP1 secretion, not by the increase of CTRP1 mRNA transcription. In addition, the levels of CTRP1 were significantly up-regulated in hypertensive patients' serum. As CTRP1 was highly expressed in obese subjects as well as up-regulated in hypertensive patients, CTRP1 may be a newly identified molecular link between obesity and hypertension.
补体 C1q 肿瘤坏死因子相关蛋白 1（CTRP1）是 CTRP 超家族的成员之一，在肥胖的 Zucker 糖尿病脂肪（fa/fa）大鼠的脂肪组织中高水平表达，并且 CTRP1 的表达由促炎细胞因子诱导，包括肿瘤坏死因子-α和白细胞介素-1β。在本研究中，我们研究了 CTRP1 对醛固酮生成的刺激作用，因为观察到 CTRP1 在醛固酮产生部位肾上腺皮质的球状带中特异性表达。CTRP1 对人肾上腺皮质细胞系 H295R 细胞中醛固酮生成的增加呈剂量依赖性。检测醛固酮合成酶 CYP11B2 的表达水平以研究 CTRP1 增强醛固酮生成的分子机制。用 CTRP1 处理后，CYP11B2 的表达以及在刺激 CYP11B2 基因表达中起关键作用的转录因子 NGFIB 和 NURR1 的表达均大幅增加。还发现血管紧张素 II 诱导的醛固酮生成至少部分是由 CTRP1 分泌的刺激介导的，而不是由 CTRP1 mRNA 转录的增加介导的。此外，高血压患者血清中 CTRP1 的水平显著上调。由于 CTRP1 在肥胖受试者中高表达且在高血压患者中上调，CTRP1 可能是肥胖与高血压之间新发现的分子联系。
