High glucose instigates tubulointerstitial injury by stimulating hetero-dimerization of adiponectin and angiotensin II receptors
High glucose instigates tubulointerstitial injury by stimulating hetero-dimerization of adiponectin and angiotensin II receptors
复制标题
高葡萄糖通过刺激脂联素和血管紧张素 II 受体的异二聚化引起肾小管间质损伤
DOI：
10.1016/j.bbrc.2017.08.047
复制
发表时间：
2017-11-04
影响因子：
3.1
通讯作者：
Wu, Xiaoyan
中科院分区：
文献类型：
--
作者：
Zha, Dongqing;Cheng, Huaiyan;Wu, Xiaoyan
脂联素及其相关受体的异常表达和功能障碍与糖尿病和糖尿病肾病（DKD）有关，而血管紧张素受体阻滞剂（ARB）和血管紧张素转换酶抑制剂（ACEIs）通过上调脂联素表达缓解糖尿病蛋白尿并预防DKD的发展。在这里，我们报告，高糖刺激血管紧张素II（AngII）受体（AT 1和AT 2）在肾近端肾小管上皮细胞（NRK-52 E）的表达。这些受体分别与脂联素受体AdipoR 1和AdipoR 2发生异源二聚化。高糖抑制AT 1和AT 2的二聚化。有趣的是，这些异源二聚体通过抑制脂联素受体的细胞保护作用引起肾小管间质损伤。这些受体-受体异源二聚化模式可能参与高糖诱导的肾小管间质损伤，并可能成为潜在的治疗靶点。(C)2017由Elsevier Inc.出版
Abnormal expression and dysfunction of adiponectin and the cognate receptors are involved in diabetes and diabetic kidney disease (DKD), whereas angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) alleviate diabetic albuminuria and prevent development of DKD through upregulation of adiponectin expression. Here we report that high glucose stimulates expression of angiotensin II (AngII) receptors (AT1 and AT2) in renal proximal tubular epithelial cells (NRK-52E). These receptors underwent hetero-dimerization with adiponectin receptor AdipoR1 and AdipoR2, respectively. High glucose inhibited the dimerization between AT1 and AT2. Interestingly, these hetero-dimers instigated tubulointerstitial injury by inhibiting the cytoprotective action of the adiponectin receptors. These modes of receptor-receptor hetero-dimerization may contribute to high glucose induced renal tubulointerstitial injury and could be potential therapeutic targets. (C) 2017 Published by Elsevier Inc.