MicroRNA in the Exosomes Mediated by Resveratrol to Activate Neuronal Cells

Overview

Journal Toxics

Date 2024 Feb 23

PMID 38393218

Authors

Zhendong Zhang

Qi Tao

Lixia Bai

Zhe Qin

Xiwang Liu

Shihong Li

Yajun Yang

Wenbo Ge

Jianyong Li

Affiliations

Soon will be listed here.

Abstract

Resveratrol (RSV), a polyphenol, is known to have a wide range of pharmacological properties in vitro. RSV may have therapeutic value for various neurodegenerative diseases via neuroprotective effects. However, it is not yet clear whether RSV can induce intestinal-brain interactions. It is assumed that the intestinal cells may secrete some factors after being stimulated by other substances. These secreted factors may activate nerve cells through gut-brain interaction, such as exosomes. In this study, it was discovered that Caco-2 cells treated with RSV secrete exosomes to activate SH-SY5Y neuronal cells. The results showed that secreted factors from RSV-treated Caco-2 cells activated SH-SY5Y. The exosomes of RSV-treated Caco-2 cells activated SH-SY5Y cells, which was manifested in the lengthening of the nerve filaments of SH-SY5Y cells. The exosomes were characterized using transmission electron microscopy and sequenced using the Illumina NovaSeq 6000 sequencer. The results showed that the miRNA expression profile of exosomes after RSV treatment changed, and twenty-six kinds of miRNAs were identified which expressed differentially between the control group and the RSV-treated group. Among them, three miRNAs were selected as candidate genes for inducing SH-SY5Y neural cell activation. Three miRNA mimics could activate SH-SY5Y neurons. These results suggested that the miRNA in intestinal exocrine cells treated with RSV may play an important role in the activation of SH-SY5Y neurons.

References

Sugihara Y, Onoue S, Tashiro K, Sato M, Hasegawa T, Katakura Y . Carnosine induces intestinal cells to secrete exosomes that activate neuronal cells. PLoS One. 2019; 14(5):e0217394. PMC: 6538158. DOI: 10.1371/journal.pone.0217394. View

Guo F, Parker Kerrigan B, Yang D, Hu L, Shmulevich I, Sood A . Post-transcriptional regulatory network of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions. J Hematol Oncol. 2014; 7:19. PMC: 3973872. DOI: 10.1186/1756-8722-7-19. View

Lu K, Chiou R, Chen L, Chen M, Tseng W, Hsieh H . Neuroprotective effects of resveratrol on cerebral ischemia-induced neuron loss mediated by free radical scavenging and cerebral blood flow elevation. J Agric Food Chem. 2006; 54(8):3126-31. DOI: 10.1021/jf053011q. View

Zhang Q, Huang H, Zheng F, Liu H, Qiu F, Chen Y . Resveratrol exerts antitumor effects by downregulating CD8CD122 Tregs in murine hepatocellular carcinoma. Oncoimmunology. 2020; 9(1):1829346. PMC: 7588216. DOI: 10.1080/2162402X.2020.1829346. View

Inotsuka R, Uchimura K, Yamatsu A, Kim M, Katakura Y . γ-Aminobutyric acid (GABA) activates neuronal cells by inducing the secretion of exosomes from intestinal cells. Food Funct. 2020; 11(10):9285-9290. DOI: 10.1039/d0fo01184c. View

Liu Z, Xu J, Wu X, Wang Y, Lin Y, Wu D . Molecular Analysis of UV-C Induced Resveratrol Accumulation in Leaves. Int J Mol Sci. 2019; 20(24). PMC: 6940797. DOI: 10.3390/ijms20246185. View

Yon J, Kim Y, Park D . The Ethanol Fraction of White Rose Petal Extract Abrogates Excitotoxicity-Induced Neuronal Damage and through Inhibition of Oxidative Stress and Proinflammation. Nutrients. 2018; 10(10). PMC: 6213719. DOI: 10.3390/nu10101375. View

Rehman A, Khan P, Maurya S, Siddiqui J, Santamaria-Barria J, Batra S . Liquid biopsies to occult brain metastasis. Mol Cancer. 2022; 21(1):113. PMC: 9088117. DOI: 10.1186/s12943-022-01577-x. View

Penumathsa S, Thirunavukkarasu M, Koneru S, Juhasz B, Zhan L, Pant R . Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat. J Mol Cell Cardiol. 2006; 42(3):508-16. PMC: 1857339. DOI: 10.1016/j.yjmcc.2006.10.018. View

10.

Ates O, Cayli S, Yucel N, Altinoz E, Kocak A, Durak M . Central nervous system protection by resveratrol in streptozotocin-induced diabetic rats. J Clin Neurosci. 2007; 14(3):256-60. DOI: 10.1016/j.jocn.2005.12.010. View

11.

Liu T, Zang N, Zhou N, Li W, Xie X, Deng Y . Resveratrol inhibits the TRIF-dependent pathway by upregulating sterile alpha and armadillo motif protein, contributing to anti-inflammatory effects after respiratory syncytial virus infection. J Virol. 2014; 88(8):4229-36. PMC: 3993725. DOI: 10.1128/JVI.03637-13. View

12.

Ano Y, Takaichi Y, Uchida K, Kondo K, Nakayama H, Takashima A . Iso-α-Acids, the Bitter Components of Beer, Suppress Microglial Inflammation in rTg4510 Tauopathy. Molecules. 2018; 23(12). PMC: 6321553. DOI: 10.3390/molecules23123133. View

13.

Machado N, Gutierrez G, Matos M, Fernandez M . Preservation of the Antioxidant Capacity of Resveratrol via Encapsulation in Niosomes. Foods. 2021; 10(5). PMC: 8147147. DOI: 10.3390/foods10050988. View

14.

Zhuang H, Kim Y, Koehler R, Dore S . Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann N Y Acad Sci. 2003; 993:276-86; discussion 287-8. DOI: 10.1111/j.1749-6632.2003.tb07534.x. View

15.

Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood M . Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011; 29(4):341-5. DOI: 10.1038/nbt.1807. View

16.

Xiao Y, Qin T, Sun L, Qian W, Li J, Duan W . Resveratrol Ameliorates the Malignant Progression of Pancreatic Cancer by Inhibiting Hypoxia-induced Pancreatic Stellate Cell Activation. Cell Transplant. 2020; 29:963689720929987. PMC: 7563930. DOI: 10.1177/0963689720929987. View

17.

Zempleni J, Sukreet S, Zhou F, Wu D, Mutai E . Milk-Derived Exosomes and Metabolic Regulation. Annu Rev Anim Biosci. 2018; 7:245-262. DOI: 10.1146/annurev-animal-020518-115300. View

18.

Toro M, Nowomiejska K, Avitabile T, Rejdak R, Tripodi S, Porta A . Effect of Resveratrol on In Vitro and In Vivo Models of Diabetic Retinophathy: A Systematic Review. Int J Mol Sci. 2019; 20(14). PMC: 6678653. DOI: 10.3390/ijms20143503. View

19.

Gong Y, Wang C, Jiang Y, Zhang S, Feng S, Fu Y . Metformin Inhibits Tumor Metastasis through Suppressing Hsp90α Secretion in an AMPKα1-PKCγ Dependent Manner. Cells. 2020; 9(1). PMC: 7016760. DOI: 10.3390/cells9010144. View

20.

Record M, Subra C, Silvente-Poirot S, Poirot M . Exosomes as intercellular signalosomes and pharmacological effectors. Biochem Pharmacol. 2011; 81(10):1171-82. DOI: 10.1016/j.bcp.2011.02.011. View