Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice.
Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice.
复制标题
DOI：
10.3390/ijms222212432
复制
发表时间：
2021-11-18
影响因子：
5.6
通讯作者：
Tamura K
中科院分区：
文献类型：
--
作者：
Urate S;Wakui H;Azushima K;Yamaji T;Suzuki T;Abe E;Tanaka S;Taguchi S;Tsukamoto S;Kinguchi S;Uneda K;Kanaoka T;Atobe Y;Funakoshi K;Yamashita A;Tamura K
肾脏是最容易受到年龄相关损伤的器官之一。一般认为，肾脏衰老伴随着肾脏纤维化，是慢性肾脏疾病的最终共同途径。马兜铃酸(AA)是一种肾毒性物质，可引起AA肾病(AAN)，其特征是进行性肾脏纤维化和功能下降。虽然肾纤维化与肾脏老化有关，但AA是否会导致肾脏衰老仍不清楚。本研究的目的是探讨AAN作为肾脏老化模型的潜在用途。在这里，我们通过给C57BL/6小鼠长期服用AA来检测AAN模型中的衰老相关因素。与对照组相比，AA组表现出肾脏衰老的表型，如肾萎缩、肾功能下降和肾小管间质纤维化。此外，AA促进了肾脏细胞的衰老，并增加了肾脏p16mRNA的表达和衰老相关的β半乳糖苷酶活性。此外，AA处理的小鼠表现出近端小管线粒体异常，以及活性氧积累。抗衰老基因klotho在AA处理的小鼠肾脏中也显著减少。总而言之，本研究的结果表明，AA改变衰老相关因素，肾脏纤维化与肾脏衰老密切相关。
The kidney is one of the most susceptible organs to age-related impairments. Generally, renal aging is accompanied by renal fibrosis, which is the final common pathway of chronic kidney diseases. Aristolochic acid (AA), a nephrotoxic agent, causes AA nephropathy (AAN), which is characterized by progressive renal fibrosis and functional decline. Although renal fibrosis is associated with renal aging, whether AA induces renal aging remains unclear. The aim of the present study is to investigate the potential use of AAN as a model of renal aging. Here, we examined senescence-related factors in AAN models by chronically administering AA to C57BL/6 mice. Compared with controls, the AA group demonstrated aging kidney phenotypes, such as renal atrophy, renal functional decline, and tubulointerstitial fibrosis. Additionally, AA promoted cellular senescence specifically in the kidneys, and increased renal p16 mRNA expression and senescence-associated β-galactosidase activity. Furthermore, AA-treated mice exhibited proximal tubular mitochondrial abnormalities, as well as reactive oxygen species accumulation. Klotho, an antiaging gene, was also significantly decreased in the kidneys of AA-treated mice. Collectively, the results of the present study indicate that AA alters senescence-related factors, and that renal fibrosis is closely related to renal aging.
登录
查看更多内容
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
8.3
作者：
Shigenaga, Atsu-ichiro;Tamura, Kouichi;Umemura, Satoshi
通讯作者：
Umemura, Satoshi
影响因子：
--
作者：
Zuo, Zhong;Lei, Han;Sun, Zhongjie
通讯作者：
Sun, Zhongjie
影响因子：
4.6
作者：
Tsukamoto S;Wakui H;Azushima K;Yamaji T;Urate S;Suzuki T;Abe E;Tanaka S;Taguchi S;Yamada T;Kinguchi S;Kamimura D;Yamashita A;Sano D;Nakano M;Hashimoto T;Tamura K
通讯作者：
Tamura K
DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF