title: Plasma-specific microRNA response induced by acute exposure to aristolochic acid I in rats.
abstract: Aristolochic acid I (AAI) derived from a natural herbal alkaloid is a nephrotoxicant. AAI-induced acute kidney injury (AKI), a devastating clinical disease associated with high mortality rates, is difficult for early diagnosis. To address this issue, we identified and validated early-detection biomarkers for AAI-induced acute kidney injury via profiling microRNA expression in rats. Global miRNA expression profile analysis found that 21 miRNAs were significantly dysregulated in kidney of rats treated by 40 mg/kg AAI on day 2, day 4, or day 6, among which 5 miRNAs were upregulated at all three time points. Quantitative RT-PCR confirmed that miR-21-3p on day 4 and day 6 was obviously upregulated in kidney of rats treated by 40 mg/kg AAI. Further examination found that miR-21-3p was increased in plasma early on day 2 in 10 mg/kg AAI-treated rats, but not in non-target organs. Importantly, the elevation of plasma miR-21-3p preceded the increase in blood urea nitrogen and creatinine, and the presence of renal tubular injury, characterized by differential increase before and after the presence of renal tubular lesions. Our findings thus show that miRNA expression is upregulated in kidney and plasma of AKI rat induced by AAI, and plasma miR-21-3p may be served as a new potential biomarker for early diagnosing AAI-induced acute kidney injury in rats, and possibly in humans.
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Room 1403, No. 1 Building, 1200 Cai Lun Road, Zhangjiang, Pudong, Shanghai, 201203, People's Republic of China.
authors.forename: Xue-Yan
authors.initials: XY
authors.lastname: Pu
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Room 1403, No. 1 Building, 1200 Cai Lun Road, Zhangjiang, Pudong, Shanghai, 201203, People's Republic of China.
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Shen
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Room 1403, No. 1 Building, 1200 Cai Lun Road, Zhangjiang, Pudong, Shanghai, 201203, People's Republic of China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Deng
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Room 1403, No. 1 Building, 1200 Cai Lun Road, Zhangjiang, Pudong, Shanghai, 201203, People's Republic of China. zza@shutcm.edu.cn.
authors.forename: Ze-An
authors.identifier: http://orcid.org/0000-0003-3677-8060
authors.initials: ZA
authors.lastname: Zhang
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D000818:Animals; D034341:Aristolochic Acids / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D025341:Principal Component Analysis; D017208:Rats, Wistar; D015203:Reproducibility of Results; D023382:Toxicity Tests, Acute / Q000379:methods
chemical_list: D034341:Aristolochic Acids; D015415:Biomarkers; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C000228:aristolochic acid I; D003404:Creatinine
keywords: Acute kidney injury; Acute toxicity; Aristolochic acid I; Biomarker; Rats; microRNA