缺氧通过HIF-1α/NF-κB通路诱导肾小管上皮细胞C3aR表达（英文）  

Hypoxia Induced C3a Receptor Expression in Tubular Epithelial Cell Through HIF-1α/NF-κB Pathway

作　　者：赵文紧[1] 陈德君[2] 李丽娟[1] 郑敬民[1] 

机构地区：[1]南京军区南京总医院国家肾脏疾病临床医学研究中心全军肾脏病研究所,南京210002 [2]恩泽医疗中心浙江省台州医院,临海317000

出　　处：《生物化学与生物物理进展》2017年第11期999-1006,共8页Progress In Biochemistry and Biophysics

基　　金：supported by a grant from The National Natural Science Foundation of China(81370828)~~

摘　　要：C3aR是补体C3a的受体.在肾脏,已发现C3aR表达于包括肾小管上皮细胞在内的多种细胞.在特定的病理情况下,C3aR表达上调并参与多种肾脏疾病的病理过程,但有关C3aR在肾脏细胞中的表达调控机制仍不清楚.小管间质缺氧是肾脏疾病中的一种常见现象,也是一种重要致病因素.为了探讨缺氧对C3aR的表达调控作用,本文利用体外缺氧模型,对模型条件下C3aR在肾小管上皮细胞中的表达变化情况进行了分析,同时检测了HIF-1α和NF-κB的表达变化及活化情况,以及HIF-1α和NF-κB抑制剂对C3aR的表达影响情况.结果发现缺氧可诱导C3aR mRNA及蛋白质水平的表达上调、HIF-1α和NF-κB的核转移.HIF-1α和NF-κB抑制剂可阻断缺氧对C3aR的诱导作用,且HIF-1α抑制剂可抑制NF-κB的核转移.这些结果说明缺氧可通过HIF-1α/NF-κB通路诱导肾小管上皮细胞C3aR的表达.考虑到C3aR活化可促进肾小管的损伤,我们推测C3aR通路可能参与了缺氧和NF-κB诱导的肾小管损伤过程,可能是防治缺氧和NF-κB诱导肾组织损伤的一个新靶标.The anaphylatoxin C3a specific receptor C3aR plays a critical role in the renal diseases, but little is known about the regulation of C3aR expression. Tubulointerstitial hypoxia is common in kidney diseases and is an important pathogenic factor contributing to renal injuries. To investigate whether hypoxia is involved in the regulation of C3aR expression in tubular epithelial cell, in the present study, we investigated the effect of hypoxia on C3aR expression and the underlying mechanism. The human proximal tubular epithelial cells （HK-2） were cultured in hypoxic condition mimicked by addition of NaN3. The mRNA expression of C3aR was analyzed by quantitative real-time PCR; the protein level of C3aR was evaluated by Western blotting and immunofluorescence. The levels of HIF-1α and NF-κB in nucleus, as well as the effect of HIF-1α or NF-κB inhibition on the expression of C3aR were also examined. We found that hypoxia induced upregulation of C3aR expression both in mRNA and protein level. The protein levels of HIF-1α and NF-κB in nucleus were increased in hypoxic condition. Pre-incubation with HIF-1α or NF-κB inhibitor, both inhibited the C3aR mRNA and protein expression induced by hypoxia. In addition, supplementation with HIF-1α inhibitor decreased the nuclear translocation of NF-κB. These results indicated that hypoxia could induce the expression of C3aR in tubular epithelial cells through HIF- 1αNF-κB pathway.

关 键 词：缺氧 C3aR HIF-1Α NF-ΚB 表达 

分 类 号：R394[医药卫生—医学遗传学]