Stress Signal Network between Hypoxia and ER Stress in Chronic Kidney Disease.
Stress Signal Network between Hypoxia and ER Stress in Chronic Kidney Disease.
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DOI：
10.3389/fphys.2017.00074
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发表时间：
2017
影响因子：
4
通讯作者：
Inagi R
中科院分区：
文献类型：
--
作者：
Maekawa H;Inagi R
慢性肾脏疾病(CKD)的特征是肾功能不可逆转地下降，并导致各种代谢功能障碍。积累的研究结果表明，慢性低氧应激和内质网应激参与了一系列的致病条件，包括CKD的进展。由于动静脉氧分流的存在，肾脏被认为容易受到缺氧的影响。慢性肾脏缺氧是由多种致病因素引起的，包括肾缺血、肾小管周围毛细血管减少和肾小管间质纤维化。内质网是一个细胞器，通过未折叠蛋白反应(UPR)途径帮助维持蛋白质的质量，与非适应性UPR激活相关的内质网功能障碍称为内质网应激。据报道，内质网应激与肾脏发病的一些影响有关，特别是在足细胞裂隙横隔膜和肾小管间质。此外，慢性低氧通过氧化应激、表观遗传学改变、脂质代谢和AKT途径等多种机制介导血管内皮细胞和肾小管间质的内质网应激。总而言之，越来越多的共识认为，这些应激通过复杂的应激信号网络相互作用，从而导致CKD的恶化(图1)。这种应激信号网络可能是旨在改善慢性肾脏病的干预措施的靶点。
Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney function and induction of various metabolic dysfunctions. Accumulated findings reveal that chronic hypoxic stress and endoplasmic reticulum (ER) stress are involved in a range of pathogenic conditions, including the progression of CKD. Because of the presence of an arteriovenous oxygen shunt, the kidney is thought to be susceptible to hypoxia. Chronic kidney hypoxia is induced by a number of pathogenic conditions, including renal ischemia, reduced peritubular capillary, and tubulointerstitial fibrosis. The ER is an organelle which helps maintain the quality of proteins through the unfolded protein response (UPR) pathway, and ER dysfunction associated with maladaptive UPR activation is named ER stress. ER stress is reported to be related to some of the effects of pathogenesis in kidney, particularly in the podocyte slit diaphragm and tubulointerstitium. Furthermore, chronic hypoxia mediates ER stress in blood vessel endothelial cells and tubulointerstitium via several mechanisms, including oxidative stress, epigenetic alteration, lipid metabolism, and the AKT pathway. In summary, a growing consensus considers that these stresses interact via complicated stress signal networks, which leads to the exacerbation of CKD (Figure 1). This stress signal network might be a target for interventions aimed at ameliorating CKD.