Resveratrol Mitigates Uremic Toxin-Induced Intestinal Barrier Dysfunction in Chronic Kidney Disease by Promoting Mitophagy and Inhibiting Apoptosis Pathways

被引:2
作者
Zheng, Cai-Mei [1 ,2 ,3 ]
Hou, Yi-Chou [4 ]
Tsai, Kuo-Wang [5 ]
Hu, Wan-Chung [6 ]
Yang, Hsiu-Chien [7 ,8 ]
Liao, Min-Tser [9 ,10 ]
Lu, Kuo-Cheng [11 ,12 ]
机构
[1] Taipei Med Univ, Shuang Ho Hosp, Dept Internal Med, Div Nephrol, New Taipei City, Taiwan
[2] Taipei Med Univ, Coll Med, Sch Med, Dept Internal Med,Div Nephrol, Taipei, Taiwan
[3] Taipei Med Univ, TMU Res Ctr Urol & Kidney, Taipei, Taiwan
[4] Fu Jen Catholic Univ, Cardinal Tien Hosp, Sch Med, Div Nephrol,Dept Internal Med, New Taipei City, Taiwan
[5] Taipei Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Med Res, New Taipei City, Taiwan
[6] Taipei Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Clin Pathol & Med Res, New Taipei City 231, Taiwan
[7] Zuoying Branch Kaohsiung Armed Forces Gen Hosp, Dept Internal Med, Div Nephrol, Kaohsiung 813, Taiwan
[8] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Med, Div Nephrol, Taipei 114, Taiwan
[9] Taoyuan Armed Forces Gen Hosp, Dept Pediat, Taoyuan 325, Taiwan
[10] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Pediat, Taipei 114, Taiwan
[11] Taipei Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Med, Div Nephrol, New Taipei City, Taiwan
[12] Fu Jen Catholic Univ Hosp, Fu Jen Catholic Univ, Sch Med, Div Nephrol,Dept Med, New Taipei City, Taiwan
来源
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES | 2024年 / 21卷 / 13期
关键词
indoxyl sulfate; resveratrol; intestinal barrier; tight junction proteins; mitophagy; apoptosis; autophagy; SULFATE;
D O I
10.7150/ijms.100963
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Chronic Kidney Disease (CKD) is a systemic progressive disorder related to uremic toxins. Uremic toxins disturb intestinal epithelial destruction and barrier dysfunction leading to gut-renal axis disorders in CKD. We examine the protective role of Resveratrol (RSV) against uremic toxin indoxyl sulphate (IS) related intestinal barrier disturbances among CKD. Methods: 5/6 nephrectomized mice and isolated primary mouse intestinal epithelial cells (IEC-6) are used to assess the influence of IS on intestinal epithelial tight junction barriers. Serum biochemistry parameters, hematoxylin & eosin (H&E) and immunohistochemistry staining (IHC), Western blot analysis, q-PCR, and si-RNA targeted against AhR were used in this study. Results: IS decreases the expression of tight junction proteins (TJPs) ZO-1 and claudins, increases the apoptosis and impairs mitophagy within IECs. Treatment with RSV not only reduces the loss of TJPs but also modulates mitophagy markers LC3 and P62, and concurrently decreases the levels of apoptosis-related proteins. Significantly, RSV ameliorates intestinal barrier dysfunction in CKD by modulating mitophagy via the IRF1-DRP1 axis, restoring autophagy, and inhibiting apoptosis through the activation of the PI3K/Akt-Ho-1 anti-oxidant pathway, and mTOR regulated pathways. Conclusion: This study establishes RSV as a potential therapeutic agent that can ameliorate gut-renal axis disturbances in CKD. These findings provide valuable insights into mechanisms underlying RSV RSV-mediated gut-renal axis, highlighting its effectiveness as a potential treatment option for CKD-associated intestinal barrier dysfunction.
引用
收藏
页码:2437 / 2449
页数:13
相关论文
共 38 条
  • [1] Amelioration of oxidative stress-mediated apoptosis in copper oxide nanoparticles-induced liver injury in rats by potent antioxidants
    Abdelazeim, Samy A.
    Shehata, Nagwa Ibrahim
    Aly, Hanan Farouk
    Shams, Shams Gamal Eldin
    [J]. SCIENTIFIC REPORTS, 2020, 10 (01)
  • [2] Cardiovascular and Antiobesity Effects of Resveratrol Mediated through the Gut Microbiota
    Bird, Julia K.
    Raederstorff, Daniel
    Weber, Peter
    Steinert, Robert E.
    [J]. ADVANCES IN NUTRITION, 2017, 8 (06) : 839 - 849
  • [3] Beneficial Effects of Concentrated Growth Factors and Resveratrol on Human Osteoblasts In Vitro Treated with Bisphosphonates
    Borsani, Elisa
    Bonazza, Veronica
    Buffoli, Barbara
    Nocini, Pier Francesco
    Albanese, Massimo
    Zotti, Francesca
    Inchingolo, Francesco
    Rezzani, Rita
    Rodella, Luigi F.
    [J]. BIOMED RESEARCH INTERNATIONAL, 2018, 2018
  • [4] Effect of resveratrol on intestinal tight junction proteins and the gut microbiome in high-fat diet-fed insulin resistant mice
    Chen, Kaiting
    Zhao, Hang
    Shu, Linyi
    Xing, Hanying
    Wang, Chao
    Lu, Caiping
    Song, Guangyao
    [J]. INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION, 2020, 71 (08) : 965 - 978
  • [5] Role of Mitochondria in Intestinal Epithelial Barrier Dysfunction in Inflammatory Bowel Disease
    Chernyavskij, D. A.
    Galkin, I. I.
    Pavlyuchenkova, A. N.
    Fedorov, A. V.
    Chelombitko, M. A.
    [J]. MOLECULAR BIOLOGY, 2023, 57 (06) : 1024 - 1037
  • [6] Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism
    Ding, Lin
    Chang, Mengru
    Guo, Ying
    Zhang, Lingyu
    Xue, Changhu
    Yanagita, Teruyoshi
    Zhang, Tiantian
    Wang, Yuming
    [J]. LIPIDS IN HEALTH AND DISEASE, 2018, 17
  • [7] The gut-kidney axis
    Evenepoel, Pieter
    Poesen, Ruben
    Meijers, Bjorn
    [J]. PEDIATRIC NEPHROLOGY, 2017, 32 (11) : 2005 - 2014
  • [8] Heme oxygenase-1 contributes to the protective effect of resveratrol against endothelial dysfunction in STZ-induced diabetes in rats
    Hammad, Asmaa S. A.
    Ahmed, Al-Shaimaa F.
    Heeba, Gehan H.
    Taye, Ashraf
    [J]. LIFE SCIENCES, 2019, 239
  • [9] Mitochondrial function and gastrointestinal diseases
    Haque, Parsa S.
    Kapur, Neeraj
    Barrett, Terrence A.
    Theiss, Arianne L.
    [J]. NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2024, 21 (08) : 537 - 555
  • [10] Indoxyl sulfate induces intestinal barrier injury through IRF1-DRP1 axis -mediated mitophagy impairment
    Huang, Yinghui
    Zhou, Jie
    Wang, Shaobo
    Xiong, Jiachuan
    Chen, Yin
    Liu, Yong
    Xiao, Tangli
    Li, Yi
    He, Ting
    Li, Yan
    Bi, Xianjin
    Yang, Ke
    Han, Wenhao
    Qiao, Yu
    Yu, Yanli
    Zhao, Jinghong
    [J]. THERANOSTICS, 2020, 10 (16): : 7384 - 7400