Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice
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 prog...
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MDPI AG
2021
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oai:doaj.org-article:045f894d93e7448a9509537adb128ec42021-11-25T17:56:35ZAristolochic Acid Induces Renal Fibrosis and Senescence in Mice10.3390/ijms2222124321422-00671661-6596https://doaj.org/article/045f894d93e7448a9509537adb128ec42021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12432https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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.Shingo UrateHiromichi WakuiKengo AzushimaTakahiro YamajiToru SuzukiEriko AbeShohei TanakaShinya TaguchiShunichiro TsukamotoSho KinguchiKazushi UnedaTomohiko KanaokaYoshitoshi AtobeKengo FunakoshiAkio YamashitaKouichi TamuraMDPI AGarticlechronic kidney diseaserenal fibrosisaristolochic acidagingcellular senescenceBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12432, p 12432 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
chronic kidney disease renal fibrosis aristolochic acid aging cellular senescence Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
chronic kidney disease renal fibrosis aristolochic acid aging cellular senescence Biology (General) QH301-705.5 Chemistry QD1-999 Shingo Urate Hiromichi Wakui Kengo Azushima Takahiro Yamaji Toru Suzuki Eriko Abe Shohei Tanaka Shinya Taguchi Shunichiro Tsukamoto Sho Kinguchi Kazushi Uneda Tomohiko Kanaoka Yoshitoshi Atobe Kengo Funakoshi Akio Yamashita Kouichi Tamura Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice |
| description |
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. |
| format |
article |
| author |
Shingo Urate Hiromichi Wakui Kengo Azushima Takahiro Yamaji Toru Suzuki Eriko Abe Shohei Tanaka Shinya Taguchi Shunichiro Tsukamoto Sho Kinguchi Kazushi Uneda Tomohiko Kanaoka Yoshitoshi Atobe Kengo Funakoshi Akio Yamashita Kouichi Tamura |
| author_facet |
Shingo Urate Hiromichi Wakui Kengo Azushima Takahiro Yamaji Toru Suzuki Eriko Abe Shohei Tanaka Shinya Taguchi Shunichiro Tsukamoto Sho Kinguchi Kazushi Uneda Tomohiko Kanaoka Yoshitoshi Atobe Kengo Funakoshi Akio Yamashita Kouichi Tamura |
| author_sort |
Shingo Urate |
| title |
Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice |
| title_short |
Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice |
| title_full |
Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice |
| title_fullStr |
Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice |
| title_full_unstemmed |
Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice |
| title_sort |
aristolochic acid induces renal fibrosis and senescence in mice |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/045f894d93e7448a9509537adb128ec4 |
| work_keys_str_mv |
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