Hydroxychloroquine alleviates renal interstitial fibrosis by inhibiting the PI3K/Akt signaling pathway
Hydroxychloroquine alleviates renal interstitial fibrosis by inhibiting the PI3K/Akt signaling pathway
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DOI：
10.1016/j.bbrc.2022.04.058
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发表时间：
2022-04-21
影响因子：
3.1
通讯作者：
Yang, Xiangdong
中科院分区：
文献类型：
--
作者：
Li, Dengren;Yu, Kuipeng;Yang, Xiangdong
肾纤维化是慢性肾脏疾病的最终表现，其进展为终末期肾脏疾病。羟氯喹（HCQ）已被用于治疗自身免疫性疾病，但HCQ在肾纤维化中的潜在作用机制仍不清楚。C57 BL/6 J小鼠随机分为假手术组、UUO组和UUO刺HCQ组（20 mg/kg）。HE和Masson染色观察肾组织损伤和纤维化情况，Western blotting检测上皮-间质转化（EMT）、细胞外基质（ECM）、PI 3 K/AKT和NF-κ B相关蛋白的表达。采用PCR和TUNEL法检测炎症因子和细胞凋亡。用TGF-β 1处理的HK-2细胞用于体外实验。HCQ可能对通过122个靶基因介导的肾纤维化具有潜在的治疗作用，并且这些基因的京都基因和基因组途径百科全书基于网络药理学富集了PI 3 K/AKT信号传导。接受HCQ的UUO小鼠表现出比UUO小鼠显著更少的肾小管损伤。HCQ处理还减弱了UUO肾脏和TGF β 1处理的肾小管上皮细胞中的EMT，并减轻了肾组织中的ECM沉积。此外，HCQ治疗减少UUO诱导的炎症和细胞凋亡。从机制上讲，HCQ治疗抑制了PI 3 K/Akt和NF-kB途径的激活。本研究表明，HCQ通过抑制PI 3 K/AKT和NF-kB信号通路，减轻炎症因子和肾小管上皮细胞凋亡功能，从而改善肾纤维化，为HCQ治疗肾纤维化提供了新的理论依据。(c)2022作者由爱思唯尔公司出版这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Renal fibrosis is the ultimate presentation of chronic kidney disease, which progresses to end-stage renal disease. Hydroxychloroquine (HCQ) has been adapted for the treatment of autoimmune diseases; however, the potential mechanism underlying the role of HCQ in renal fibrosis remains unclear. C57BL/6 J mice were randomly divided into three groups (sham group, UUO group, and UUO thorn HCQ group (20 mg/kg)). HE and Masson staining were performed to assess kidney tissue damage and fibrosis, and western blotting was performed to assess the expression of epithelial-mesenchymal transition (EMT), extracellular matrix (ECM), PI3K/AKT, and NF-kB-related proteins. PCR and TUNEL were adopted to detect inflammatory factors and cell apoptosis. HK-2 cells treated with TGF-b1 were used for the in vitro experiments. HCQ may potentially have therapeutic effects on renal fibrosis mediated through 122 target genes, and the Kyoto Encyclopedia of Genes and Genomes pathways of these genes were enriched for PI3K/AKT signaling based on network pharmacology. UUO mice that received HCQ demonstrated significantly less tubular damage than the UUO mice. HCQ treatment additionally blunted EMT in UUO kidneys and TGFb1-treated renal tubular epithelial cells, and alleviated ECM deposition in kidney tissue. Furthermore, HCQ treatment reduced UUO-induced inflammation and apoptosis. Mechanistically, HCQ treatment suppressed the activation of the PI3K/Akt and NF-kB pathways. This study demonstrated that HCQ ameliorated renal fibrosis by inhibiting the PI3K/AKT and NF-kB signaling pathways to attenuate inflammatory factors and the apoptotic function of renal tubular epithelial cells, thus providing renewed theoretical evidence for HCQ treatment of renal fibrosis. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).