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Resveratrol increases the activation markers and changes the release of inflammatory cytokines of hepatic stellate cells

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Abstract

The phytoalexin Resveratrol (3,5,4′-trihydroxystilbene; RSV) has been related to numerous beneficial effects on health by its cytoprotection and chemoprevention activities. Liver fibrosis is characterized by the extracellular matrix accumulation after hepatic injury and can lead to cirrhosis. Hepatic stellate cells (HSC) play a crucial role during fibrogenesis and liver wound healing by changing their quiescent phenotype to an activated phenotype for protecting healthy areas from damaged areas. Strategies on promoting the activated HSC death, the quiescence return or the cellular activation stimuli decrease play an important role on reducing liver fibrosis. Here, we evaluated the RSV effects on some markers of activation in GRX, an HSC model. We further evaluated the RSV influence in the ability of GRX on releasing inflammatory mediators. RSV at 1 and 10 µM did not alter the protein content of α-SMA, collagen I and GFAP; but 50 µM increased the content of these activation-related proteins. Also, RSV did not change the myofibroblast-like morphology of GRX. Interestingly, RSV at 10 and 50 µM decreased the GRX migration and collagen-I gel contraction. Finally, we showed that RSV triggered the increase in the TNF-α and IL-10 content in culture media of GRX while the opposite occurred for the IL-6 content. Altogether, these results suggested that RSV did not decrease the activation state of GRX and oppositely, triggered a pro-activation effect at the 50 µM concentration. However, despite the increase of TNF- α in culture media, these results on IL-6 and IL-10 secretion were in accordance with the anti-inflammatory role of RSV in our model.

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Acknowledgements

C.M. de Oliveira is the recipient of a fellowship from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). This work was also supported by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico—Brazil), FAPERGS (Fundação de Amparo à Pesquisa do Rio Grande do Sul, PqG n°1009169) and PROPESQ-UFRGS. All authors would like to thank to Dr. Elena Bernard for the helpful comments in this study.

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Authors and Affiliations

  1. Departmento de Bioquímica, ICBS, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo I, Porto Alegre, RS, CEP, 90035-003, Brazil

    Cleverson Moraes de Oliveira, Leo Anderson Meira Martins, Arieli Cruz de Sousa, Ketlen da Silveira Moraes, Moema Queiroz Vieira, Bárbara Paranhos Coelho & Fátima Costa Rodrigues Guma

  2. Departamento de Fisiologia, ICBS, Universidade Federal Do Rio Grande Do Sul, Rua Sarmento Leite, Porto Alegre, RS, CEP, 500, Brazil

    Leo Anderson Meira Martins

  3. Laboratório de Pesquisa Em Biofísica Celular E Inflamação, Pontifícia Universidade Católica Do Rio Grande Do Sul (PUCRS), Porto Alegre, RS, Brazil

    Bruna Pasqualotto Costa & Jarbas Rodrigues de Oliveira

  4. Centro de Medicina Regenerativa, Faculdade de Medicina de Petrópolis, Petrópolis, RJ, Brazil

    Radovan Borojevic

  5. Centro de Microscopia E Microanálise (CMM), Universidade Federal Do Rio Grande Do Sul, Av. Bento Gonçalves, 9500 - Prédio 43.177 - Bl 1Campus do Vale, Porto Alegre, RS, CEP, 91501-970, Brazil

    Fátima Costa Rodrigues Guma

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  1. Cleverson Moraes de Oliveira
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Contributions

Wrote the paper: CMO and LAMM. Establishment of GRX cell line: RB. Collected and analysed data: CMO, LAMM, ASC, KSM, BruPC, MQV, BarPC. Supervision and Contribution to the text writing: JRO and FCRG.

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Correspondence to Cleverson Moraes de Oliveira.

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de Oliveira, C.M., Martins, L.A.M., de Sousa, A.C. et al. Resveratrol increases the activation markers and changes the release of inflammatory cytokines of hepatic stellate cells. Mol Cell Biochem 476, 649–661 (2021). https://doi.org/10.1007/s11010-020-03933-1

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