Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA 70112-2699, USA.
Mol Cell Endocrinol. 2009 Nov 13;311(1-2):24-31. doi: 10.1016/j.mce.2009.06.013. Epub 2009 Jul 5.
In human kidneys, the mechanisms underlying angiotensinogen (AGT) augmentation by interleukin 6 (IL-6) are poorly understood and the only information available is in HK-2, immortalized human renal proximal tubular epithelial cells. Therefore, the present study was performed to elucidate the effects of IL-6 on AGT expression in primary cultured human renal proximal tubular epithelial cells (RPTEC) after characterization of HK-2 and RPTEC. RPTEC showed low basal AGT mRNA (11+/-1%) and protein (7.0+/-0.9%) expression, high IL-6 receptor (IL-6R) expression (282+/-17%), and low basal NF-kappaB (43+/-7%) and STAT3 (43+/-7%) activities compared to those in HK-2. In RPTEC, AGT mRNA and protein expressions were enhanced by IL-6 (172+/-31% and 378+/-39%, respectively). This AGT augmentation was attenuated by an IL-6R antibody. STAT3 phosphorylation (366+/-55% at 30min) and translocation were enhanced by IL-6. The AGT augmentation was attenuated by a STAT3 inhibitor. These data indicate that IL-6 increases AGT expression via STAT3 pathway in RPTEC.
在人类肾脏中,白细胞介素 6(IL-6)引起血管紧张素原(AGT)增加的机制尚不清楚,并且唯一可用的信息是在 HK-2,永生化的人肾近端肾小管上皮细胞中。因此,本研究旨在阐明 IL-6 对原代培养的人肾近端肾小管上皮细胞(RPTEC)中 AGT 表达的影响,同时对 HK-2 和 RPTEC 进行了特征描述。与 HK-2 相比,RPTEC 中 AGT mRNA(11+/-1%)和蛋白(7.0+/-0.9%)表达水平较低,IL-6 受体(IL-6R)表达水平较高(282+/-17%),NF-kappaB(43+/-7%)和 STAT3(43+/-7%)的基础活性较低。在 RPTEC 中,IL-6 增强了 AGT mRNA 和蛋白的表达(分别增加了 172+/-31%和 378+/-39%)。IL-6R 抗体可减弱这种 AGT 增强作用。IL-6 增强了 STAT3 磷酸化(30min 时为 366+/-55%)和转位。STAT3 抑制剂可减弱 AGT 增强作用。这些数据表明,IL-6 通过 RPTEC 中的 STAT3 途径增加了 AGT 的表达。