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Transforming growth factor-β1 and phosphatases modulate COX-2 protein expression and TAU phosphorylation in cultured immortalized podocytes

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Abstract

Objective and design

The aim of this study is to elucidate TGF-β1 signaling pathways involved in COX-2 protein induction and modulation of TAU protein phosphorylation in cultured podocytes.

Materials, treatment and methods

In vitro cultured immortalized podocytes were stimulated with TGF-β1 in presence and absence of pharmacologic inhibitors for various signaling pathways and phosphatases. Then, COX-2 protein expression, as well as P38MAPK, AKT and TAU phosphorylation levels were evaluated by western blot analysis.

Results

TGF-β1 induction of COX-2 protein levels was completely blocked by pharmacologic inhibitors of phosphatases, P38 MAPK, or NF-қB pathways. Time course experiments showed that TGF-β1 activated p38 MAPK after 5 min of stimulation. Interestingly, podocyte co-incubated with TGF-β1, high glucose and/or PGE2 showed strong increase in p38 MAPK and AKT phosphorylation as well as COX- 2 protein expression levels. Levels of phosphorylated AKT were further reduced and levels of phosphorylated p38 were increased when PGE2 was added to the culture media. Interestingly, selective phosphatases inhibitors completely abrogated PGE2-induced P38 MAPK and TAU phosphorylation. Also, inhibition of phosphatases reversed TGF-β1–induced COX-2 protein expression either alone or when incubated with high glucose or PGE2.

Conclusion

These data suggest TGF-β1 mediates its effect in podocyte through novel signaling mechanisms including phosphatases and TAU protein phosphorylation.

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Acknowledgements

Dr Wissam H. Faour is a recipient of a grant from the Lebanese National Council for Scientific Research and an Assistant Professor of Pharmacology at the School of Medicine at the Lebanese American University. This project has been funded with support from the National Council for Scientific Research in Lebanon, Grant number: 01-08-2015.

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Authors and Affiliations

  1. Institut Européen des Membranes, Université de Montpellier, Montpellier, France

    Maya S. Abdallah

  2. Division of Nephrology, Department of Medicine, Kidney Research Centre, The Ottawa Hospital, Ottawa, ON, K1H 8M5, Canada

    Christopher R. J. Kennedy

  3. Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, PO Box 36, Byblos, Lebanon

    Maya S. Abdallah, Joseph S. Stephan, Pamela Abou Khalil & Wissam H. Faour

  4. School of Pharmacy, Lebanese American University, P.O. Box 36, Byblos, Lebanon

    Mohammad Mroueh

  5. School of Medicine, American University of Beirut, Beirut, Lebanon

    Assaad A. Eid

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  1. Maya S. Abdallah
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Correspondence to Wissam H. Faour.

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Responsible Editor: John Di Battista.

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Abdallah, M.S., Kennedy, C.R.J., Stephan, J.S. et al. Transforming growth factor-β1 and phosphatases modulate COX-2 protein expression and TAU phosphorylation in cultured immortalized podocytes. Inflamm. Res. 67, 191–201 (2018). https://doi.org/10.1007/s00011-017-1110-y

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  • DOI: https://doi.org/10.1007/s00011-017-1110-y

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