Gene expression comparison reveals distinct basal expression of HOX members and differential TNF-induced response between brain- and spinal cord-derived microvascular endothelial cells. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Molino, Yves; Jabès, Françoise; Bonnet, Amandine; Gaudin, Nicolas; Bernard, Anne; Benech, Philippe; Khrestchatisky, Michel
• Is Part Of: Journal of neuroinflammation. Volume 13:Issue 1(2016)
• Page Start: 1
• Page End: 14
• Publication Date: 2016-12
• Subjects: Microvessels -- Endothelial cells -- Vascular beds -- HOX members -- TNF-α response -- Matrix metalloproteinase (MMP); Central nervous system -- Diseases -- Periodicals; Inflammation -- Periodicals; 616.8
• DOI: 10.1186/s12974-016-0749-6
• Languages: English
• ISSNs: 1742-2094

Abstract

Abstract Background The heterogeneity of endothelial cell types underlies their remarkable ability to sub-specialize and provide specific requirements for a given vascular bed. Here, we compared rat microvascular endothelial cells (MECs) derived from the brain and spinal cord in both basal and inflammatory conditions. Methods We used whole rat genome microarrays to compare, at different time points, basal and TNF-α-induced gene expression of rat MECs from in vitro models of the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). Validation at both messenger RNA (mRNA) and protein levels was performed on freshly extracted microvessels (MVs) from the brain and spinal cord (BMVs and SCMVs, respectively), as these were considered the closest in vivo tissues to cultured MECs. Results Most of the genes encoding adhesion/tight junction molecules and known endothelial markers were similarly expressed in brain and spinal cord MECs (BMECs and SCMECs, respectively). However, one striking finding was the higher expression of severalHox genes, which encode transcription factors involved in positional identity. The differential expression ofHoxa9 andHoxb7 at the mRNA levels as well as protein levels was confirmed in BMVs and SCMVs. Although the TNF-α response was in general higher in BMECs than in SCMECs at 12 h, the opposite was observed at 48 h. Furthermore, we found that expression ofTnfrsf1a and Tnfrsf1b encoding the TNF receptor super-family member 1a/TNFR1 and 1b/TNFR2, respectively, were constitutively higher in BMVs compared to SCMVs. However, onlyTnfrsf1b was induced in SCMECs in response to TNF-α at 24 and 48 h. Conclusions Our results support a role for HOX members in defining the positional identities of MECs in vivo. Our data also suggest that the delayed transcriptional activation upon TNF-α treatment in SCMECs results from the requirement of the TNF-induced expression ofTnfrsf1b . In contrast, its high basal expression in BMECs might be sufficient to confer an immediate and efficient TNF-α response.