Zha Dongqing, Cheng Huaiyan, Li Weiwei, Wu Yizhe, Li Xiaoning, Zhang Lian, Feng Ying-Hong, Wu Xiaoyan
Division of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Dept. of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Biochem Biophys Res Commun. 2017 Nov 4;493(1):840-846. doi: 10.1016/j.bbrc.2017.08.047. Epub 2017 Sep 1.
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.
脂联素及其相关受体的异常表达和功能障碍与糖尿病及糖尿病肾病（DKD）有关，而血管紧张素受体阻滞剂（ARBs）和血管紧张素转换酶抑制剂（ACEIs）可通过上调脂联素表达来减轻糖尿病蛋白尿并预防DKD的发展。在此我们报告，高糖刺激肾近端小管上皮细胞（NRK-52E）中血管紧张素II（AngII）受体（AT1和AT2）的表达。这些受体分别与脂联素受体AdipoR1和AdipoR2发生异源二聚化。高糖抑制了AT1和AT2之间的二聚化。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而引发肾小管间质损伤。这些受体-受体异源二聚化模式可能导致高糖诱导的肾小管间质损伤，并且可能是潜在的治疗靶点。
