Endothelial Protein C Receptor Expression is Regulated by Sp1 Transcription Factor in Murine Microglia

Authors : Kemal Uğur TÜFEKCİ, Halil ATEŞ, Şermin GENÇ
Pages : 6-13
Doi:10.30621/jbachs.854244
View : 45 | Download : 11
Publication Date : 2021-02-26
Article Type : Research Paper
Abstract :Objectives: Microglial cells are the central regulators of inflammatory responses in the brain and spinal cord. In addition to surveillance during resting state, they become activated due to microbial molecules and pathological insults. Endogenously expressed Activated protein C insert ignore into journalissuearticles values(APC); is an anticoagulant molecule with anti-inflammatory and cytoprotective roles, mediated by one of its receptors, Endothelial protein C receptor insert ignore into journalissuearticles values(EPCR);. This study aimed to examine the basal and inducible expression of EPCR and unravel the regulatory mediators of its expression in microglia. Methods: We studied probable effects of Lipopolysaccharide insert ignore into journalissuearticles values(LPS);, Peptidoglycan insert ignore into journalissuearticles values(PGN);, and Polyinosinic–polycytidylic acid [Polyinsert ignore into journalissuearticles values(I:C);] on EPCR mRNA and protein levels in N9 mouse microglial cells by qPCR and flow cytometry. Then, Cyclosporin A insert ignore into journalissuearticles values(CsA); and Mithramycin A insert ignore into journalissuearticles values(MMA); were used to inhibit transcription factors in the promoter region of the EPCR gene, which are Nuclear factor of activated T-cells, cytoplasmic 1 insert ignore into journalissuearticles values(NFATC1);, and specificity protein 1 insert ignore into journalissuearticles values(Sp1);. Results: As a result, the Sp1 transcription factor’s chemical inhibition impaired the upregulating effects of LPS and PGN on EPCR expression. Conclusion: Thus, our data suggest that LPS and PGN gave rise to increased EPCR levels in microglia, mainly through the Sp1 transcription factor.
Keywords : microglia, endothelial protein c receptor, lipopolysaccharide, peptidoglycan, Sp1 transcription factor

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