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Stanniocalcin-1 通过调节 Nrf2 通路减轻对比剂诱导的急性肾损伤的线粒体质量控制。

Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway.

机构信息

Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan 410011, China.

出版信息

Oxid Med Cell Longev. 2020 Apr 12;2020:1898213. doi: 10.1155/2020/1898213. eCollection 2020.

DOI:10.1155/2020/1898213
PMID:32318235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7153002/
Abstract

Contrast-induced acute kidney injury (CI-AKI) is the third common cause of acute kidney injury (AKI), which is associated with poor short- and long-term outcomes. Currently, effective therapy strategy for CI-AKI remains lacking. Stanniocalcin-1 (STC1) is a conserved glycoprotein with antiapoptosis and anti-inflammatory functions, but the role of STC1 in controlling CI-AKI is unknown. Here, we demonstrated a protective role of STC1 in contrast-induced injury in cultured renal tubular epithelial cells and CI-AKI rat models. Recombinant human STC1 (rhSTC1) regulated mitochondrial quality control, thus suppressing contrast-induced mitochondrial damage, oxidative stress, inflammatory response, and apoptotic injury. Mechanistically, activation of the Nrf2 signaling pathway contributes critically to the renoprotective effect of STC1. Together, this study demonstrates a novel role of STC1 in preventing CI-AKI and reveals Nrf2 as a molecular target of STC1. Therefore, this study provides a promising preventive target for the treatment of CI-AKI.

摘要

对比剂诱导的急性肾损伤（CI-AKI）是急性肾损伤（AKI）的第三大常见原因，与短期和长期预后不良有关。目前，CI-AKI 的有效治疗策略仍然缺乏。斯钙素-1（STC1）是一种具有抗细胞凋亡和抗炎功能的保守糖蛋白，但 STC1 在控制 CI-AKI 中的作用尚不清楚。在这里，我们证明了 STC1 在培养的肾小管上皮细胞和 CI-AKI 大鼠模型中的对比诱导损伤中的保护作用。重组人 STC1（rhSTC1）调节线粒体质量控制，从而抑制对比诱导的线粒体损伤、氧化应激、炎症反应和细胞凋亡损伤。从机制上讲，Nrf2 信号通路的激活对 STC1 的肾保护作用至关重要。总之，这项研究表明 STC1 在预防 CI-AKI 中的新作用，并揭示 Nrf2 是 STC1 的一个分子靶点。因此，这项研究为治疗 CI-AKI 提供了一个有前途的预防靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600e/7153002/770fc9226023/OMCL2020-1898213.010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/600e/7153002/469903aa5705/OMCL2020-1898213.006.jpg
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