Effects of tauroursodeoxycholate on arsenic-induced hepatic injury in mice: A comparative transcriptomic analysis.

Autor: Zheng X; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China; Harbin Municipal Center for Disease Control and Prevention, Harbin 150056, PR China. Electronic address: zhengxiujuan0556@yeah.net., Cao J; Harbin Municipal Center for Disease Control and Prevention, Harbin 150056, PR China. Electronic address: cjbhrb@126.com., Wang H; Department of Medical, The Fourth Hospital of Harbin Medical University, Harbin 150001, PR China. Electronic address: wanghe0059@163.com., Liu L; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China; The first psychological hospital of Harbin, Harbin 150081, PR China. Electronic address: Liulele925@163.com., Jin B; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China; Department of Preventive Medicine, Qiqihar Medical University, Qiqihar 161006, PR China. Electronic address: jinbm1520@qmu.edu.cn., Zhang H; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China. Electronic address: Zzhua1215@163.com., Li M; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China. Electronic address: limingqi25@163.com., Nian S; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China. Electronic address: nian15545466873@126.com., Li H; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China. Electronic address: Lihaonan89@hotmail.com., He R; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China. Electronic address: herui55555@163.com., Wang N; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China; Department of Preventive Medicine, Qiqihar Medical University, Qiqihar 161006, PR China. Electronic address: wnn891011@sina.com., Li X; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China. Electronic address: sjklixuying@163.com., Wang K; Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, PR China; National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin 150081, PR China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin 150081, PR China; Institute of Cell Biotechnology, China and Russia Medical Research Center, Harbin Medical University, Harbin 150081, PR China. Electronic address: keweiwang0718@163.com.
Jazyk: angličtina
Zdroj: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) [J Trace Elem Med Biol] 2024 Dec; Vol. 86, pp. 127512. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1016/j.jtemb.2024.127512
Abstrakt: Background: Prolonged exposure to excessive arsenic (As) and its compounds can cause damage to multiple systems, including respiratory, cardiovascular, immune, nervous, and endocrine systems. Manifestations include changes in skin pigmentation, excessive keratosis on palms and soles, gastrointestinal symptoms, and anemia. The liver as an important detoxification organ of the body, is a significant target organ for arsenic toxicity, and liver diseases are common. So far, the molecular mechanism has not been fully elucidated. Evidence suggests that taurodeoxycholic acid (TUDCA) has a protective role in arsenic-induced liver injury. This study aims to reveal potential target genes at the transcriptional level following TUDCA intervention, providing insights for the intervention of arsenic-induced liver injury.
Methods: The TUDCA intervention model of arsenic liver injury in C57BL/6 N mice was established. The experiment was divided into two phases and lasted for 24 weeks. The phase I trial (12 weeks) was divided into control, low, middle and high groups according to the dose of As. The phaseⅡtrial (12 weeks) was administered in combination with 10 mg/L sodium arsenite (the first stage high arsenic group) and TUDCA, so subsequent groups was named with H indicating high arsenic. Divide into four groups: control group(C), TUDCA solvent control group(H-Vehicle), TUDCA combined with As group(H-TUDCA), arsenic group (As). As was ingested through free water and TUDCA was administered to mice by gavage at a dose of 0.1 mL/10 g.b.w (100 mg/kg) once a day for 12 weeks. The differential expression gene (DEG) profile was obtained from the second batch of mouse liver tissues by RNA sequencing technology. Comparative transcriptomic analysis methods were used to identify co-varying DEGs between arsenic induction and TUDCA intervention, along with their associated pathways. QRT-PCR was utilized for validation.
Results: Transcriptome results showed that 487 DEGs were identified after arsenic induction. TUDCA intervention identified 231 DEGs (p-values < 0.05 and | log2(fold change) | > 1). The comparison of "AS vs C" and "H_TUDCA vs AS" identified 65 covariant DEGs, and further screened the TUDCA pathways and related genes among these genes，six pathways and 11 genes (Ccl21a, Ccr7, Mdm2, Slc2a4, Akr1b7, Pnpla3, Dusp8, Hspa1a, Cyp7a1, Cybrd1, Trpm6) were obtained. Next, we screened for covariant DEGs among the top 50 potential hub genes in arsenic-induced DEGS, and obtained 7 (Hbb-bs, Hspa1a, Mdm2, Slc2a4, Ptk6, Egr1, and Dusp8). Finally, the intersection of Hub gene and pathway gene was selected as the target genes Dusp8, Hspa1a, Mdm2 and Slc2a4. The sequencing results showed that the mRNA expressions of Dusp8, Hspa1a and Mdm2 were significantly increased after arsenic induction, while the expression of Slc2a4 was significantly decreased (P<0.05). Conversely, TUDCA intervention reversed these DEGs changes, consistent with QRT-PCR validation results.
Conclusion: This study contributes to understanding the potential health effects of arsenic-induced liver injury, identifying new potential targets, and providing references for TUDCA intervention.
Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional other personal interest of any nature or kind in any product, service and /or company that could be constructed as influencing the position presented in, or the review of, the manuscript entitled, “Effects of Tauroursodeoxycholate on Arsenic-Induced Hepatic Injury in Mice: A Comparative Transcriptomic Analysis”.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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