Abstract
Background:The epidermis is a continuously regenerating tissue maintained by a balance between proliferation and differentiation, with imbalances resulting in skin disease. We have previously found that in mouse keratinocytes, the lipid-metabolizing enzyme phospholipase D2 (PLD2) is associated with the aquaglyceroporin, aquaporin 3 (AQP3), an efficient transporter of glycerol. Our results also show that the functional interaction of AQP3 and PLD2 results in increased levels of phosphatidylglycerol (PG) in response to an elevated extracellular calcium level, which triggers keratinocyte differentiation. Indeed, we showed that directly applying PG can promote keratinocyte differentiation.Objective:We hypothesized that the differentiative effects of this PLD2/AQP3/PG signaling cascade, in which AQP3 mediates the transport of glycerol into keratinocytes followed by its PLD2-catalyzed conversion to PG, are mediated by protein kinase CβII (PKCβII), which contains a PG-binding domain in its carboxy-terminus. Method: To test this hypothesis we used quantitative RT-PCR, western blotting and immunocytochemistry.Results:We first verified the presence of PKCβII mRNA and protein in mouse keratinocytes. Next, we found that autophosphorylated (activated) PKCβII was redistributed upon treatment of keratinocytes with PG. In the unstimulated state phosphoPKCβII was found in the cytosol and perinuclear area; treatment with PG resulted in enhanced phosphoPKCβII localization in the perinuclear area. PG also induced translocation of phosphoPKCβII to the plasma membrane. In addition, we observed that overexpression of PKCβII enhanced calcium- and PG-induced keratinocyte differentiation without affecting calcium-inhibited keratinocyte proliferation.Conclusion:These results suggest that the PG produced by the PLD2/AQP3 signaling module may function by activating PKCβII.
Highlights
The epidermis forms the mechanical and water permeability barrier of the skin, allowing terrestrial existence and protecting from various environmental insults
These results suggest that the PG produced by the phospholipase D2 (PLD2)/aquaporin 3 (AQP3) signaling module may function by activating PKCβII
To ensure that expression of the enzyme was not an artifact of culture, we demonstrated PKCβII protein expression in freshly isolated keratinocytes and epidermis (Fig. 1D), as well as mRNA expression in total skin (Fig. 1B)
Summary
The epidermis forms the mechanical and water permeability barrier of the skin, allowing terrestrial existence and protecting from various environmental insults. 60 The Open Dermatology Journal, 2017, Volume 11 damaged cells and those sloughed to the surroundings. As they move upwards into the upper epidermal layers, the keratinocytes growth arrest and differentiate, expressing different sets of genes and proteins as they become more and more differentiated. A great deal is known about the signals that regulate proliferation and differentiation, including the fact that elevated extracellular calcium concentrations trigger keratinocyte differentiation [1]. The epidermis is a continuously regenerating tissue maintained by a balance between proliferation and differentiation, with imbalances resulting in skin disease. Our results show that the functional interaction of AQP3 and PLD2 results in increased levels of phosphatidylglycerol (PG) in response to an elevated extracellular calcium level, which triggers keratinocyte differentiation. We showed that directly applying PG can promote keratinocyte differentiation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
