Endogenous pleiotrophin and midkine regulate LPS-induced glial responses

Neuroscience Letters, 2018

Rosalía Fernández-Calle, Marta Vicente-Rodríguez, Esther Gramage, Carlos de la Torre-Ortiz, Carmen Pérez-García, María P. Ramos and Gonzalo Herradón

Pleiotrophin and midkine are two endogenous molecules that regulate some neuroinflammatory processes

  • Pleiotrophin (PTN) and Midkine (MK) are two growth factors that modulate neuroinflammation. They are overexpressed with certain diseases.


  • Animal models expressing or not these molecules are exposed to different concentrations of a pro-inflammatory substance (LPS).


  • The effect is assessed by looking at whether some cell types are activated (astrocytes and microglial cells).


  • In conclusion, the regulation of astroglial responses to LPS administration is highly dependent on the levels of expression of PTN and MK.

  • Abstract

    Pleiotrophin (PTN) and Midkine (MK) are two growth factors that modulate neuroinflammation. PTN overexpression in the brain prevents LPS-induced astrocytosis in mice but potentiates microglial activation. The modest astrocytic response caused by a low dose of LPS (0.5mg/kg) is blocked in the striatum of MK-/- mice whereas microglial response is unaffected. We have now tested the effects of an intermediate dose of LPS (7.5mg/kg) in glial response in PTN-/- and MK-/- mice. We found that LPS-induced astrocytosis is prevented in prefrontal cortex and striatum of both PTN-/- and MK-/- mice. Some of the morphological changes of microglia induced by LPS tended to increase in both genotypes, particularly in PTN-/- mice. Since we previously showed that PTN potentiates LPS-induced activation of BV2 microglial cells, we tested the activation of FYN kinase, a substrate of the PTN receptor RPTPβ/ζ, and the subsequent ERK1/2 phosphorylation on LPS and PTN-treated BV2 cells. LPS effects on BV2 cells were not affected by the addition of PTN, suggesting that PTN does not recruit the FYN-MAP kinase signaling pathway in order to modulate LPS effects on microglial cells. Taking together, evidences demonstrate that regulation of astroglial responses to LPS administration are highly dependent on the levels of expression of PTN and MK. Further studies are needed to clarify the possible roles of endogenous expression of PTN and MK in LPS-induced microglial responses.

    Publication

    Rosalía Fernández-Calle, Marta Vicente-Rodríguez, Esther Gramage, Carlos de la Torre-Ortiz, Carmen Pérez-García, María P. Ramos and Gonzalo Herradón

    Endogenous pleiotrophin and midkine regulate LPS-induced glial responses

    Neuroscience Letters

    @article{fernandezcalle2018endogenous,
    title = {Endogenous pleiotrophin and midkine regulate LPS-induced glial responses},
    journal = {Neuroscience Letters},
    volume = {662},
    pages = {213-218},
    year = {2018},
    issn = {0304-3940},
    doi = {https://doi.org/10.1016/j.neulet.2017.10.038},
    url = {https://www.sciencedirect.com/science/article/pii/S0304394017308649},
    author = {Rosalía Fernández-Calle and Marta Vicente-Rodríguez and Esther Gramage and Carlos {de la Torre-Ortiz} and Carmen Pérez-García and María P. Ramos and Gonzalo Herradón},
    keywords = {Neuroinflammation, Microglia, Astrogliosis, FYN kinase, Pleiotrophin, Midkine},
    }