Ghrelin modulates intracellular signalling pathways that are critical for podocyte survival

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dc.contributor.author El Zein, Nabil
dc.contributor.author Abdallah, Maya S.
dc.contributor.author Daher, Costantine F.
dc.contributor.author Mroueh, Mohammad
dc.contributor.author Stephan, Joseph
dc.contributor.author Bahous, Sola Aoun
dc.contributor.author Eid, Assaad
dc.contributor.author Faour, Wissam H.
dc.date.accessioned 2019-06-27T08:55:58Z
dc.date.available 2019-06-27T08:55:58Z
dc.date.copyright 2019 en_US
dc.identifier.issn 1099-0844 en_US
dc.identifier.uri http://hdl.handle.net/10725/10913
dc.description.abstract Damage to podocytes is a key event in glomerulopathies. While energy dense food can contribute to kidney damage, the role of the orixegenic hormone “ghrelin” in podocyte biology is still unknown. In the present study, we investigated the effect of ghrelin on podocyte survival as well as the signalling pathways mediating ghrelin effect in immortalized cultured rat podocytes. RT‐PCR analysis revealed that GHS‐R1 is expressed in rat podocytes. Western blot analysis showed that ghrelin upregulated COX‐2 protein expression in a time and dose‐dependent manner. Additionally, ghrelin activated P38 MAPK, AKT, and ERK1/2 pathways and also induced P38 MAPK phosphorylation in high glucose conditions. Ghrelin induced ROS release and dose dependently reduced podocyte survival. Ghrelin mediated podocyte cell death was partially reversed by pharmacologically inhibiting P38 MAPK or phospholipase C (PLC). Furthermore, PLC inhibitor (U73122) inhibited ghrelin induced P38 MAPK activation. While PI3K inhibitor (LY294002) was without effect on cell survival or P38 MAPK activation, it inhibited ghrelin induced ERK1/2 phosphorylation. Finally, ghrelin induced TAU phosphorylation was reversed by pharmacologic inhibitors of either P38 MAPK or PKA. In conclusion, ghrelin activated harmful molecular pathways in podocytes that can be damaging to the glomerular filtration barrier en_US
dc.language.iso en en_US
dc.title Ghrelin modulates intracellular signalling pathways that are critical for podocyte survival en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOM en_US
dc.author.idnumber 199590020 en_US
dc.author.idnumber 201509224 en_US
dc.author.idnumber 200803754 en_US
dc.author.idnumber 200904962 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Cell Biochemistry & Function en_US
dc.journal.volume 37 en_US
dc.journal.issue 4 en_US
dc.article.pages 245-255 en_US
dc.identifier.doi https://doi.org/10.1002/cbf.3397 en_US
dc.identifier.ctation El Zein, N., Abdallah, M. S., Daher, C. F., Mroueh, M., Stephan, J., Bahous, S. A., ... & Faour, W. H. (2019). Ghrelin modulates intracellular signalling pathways that are critical for podocyte survival. Cell biochemistry and function. en_US
dc.author.email mmroueh@lau.edu.lb en_US
dc.author.email joseph.stephan@lau.edu.lb en_US
dc.author.email sola.bahous@lau.edu.lb en_US
dc.author.email wissam.faour@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://onlinelibrary.wiley.com/doi/full/10.1002/cbf.3397 en_US
dc.author.affiliation Lebanese American University en_US

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