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Transcriptome analysis of brain endothelial cells from adult EC-specific Glut1 knock-out mice as compared to wild type controls

ABSTRACT: To explore the mechanisms through which GLUT1 controls EC function, we compared transcriptomic alterations induced by loss of GLUT1 by performing RNA sequencing analysis on freshly isolated ECs from adult (8 week old) GLUT1EC-/- brains. In adult brains ECs, 1494 genes were differentially expressed between WT and GLUT1-/- ECs but we did not observe compensatory upregulation of other GLUTs. Interestingly, pathway analysis revealed that ECs from GLUT1EC-/- mice were characterized by a robust activation of inflammatory and extracellular matrix pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE141923 | GEO | 2020/06/01

REPOSITORIES: GEO

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Project description:Mice were subjected to 50 eccentric contractions (EC) or 50 isometric contractions (IC) using a non-invasive model, and then sacrificed 48 hours later. RNA from the tibialis anterior of 4 animals were pooled and then split into two groups for hybridization onto two separate Affymetrix MGU74Av2 chips. Control samples were contralateral to the exercised legs, and were only subjected to enough contractions to measure isometric torque. Eccentric contractions (ECs), in which a muscle is forced to lengthen while activated, result in muscle injury and, eventually, muscle strengthening and prevention of further injury. Although the mechanical basis of eccentric contraction-induced injury has been studied in detail, muscle's biological response is less well characterized. This study presents the development of a minimally-invasive model of EC injury in the mouse, follows the time course of torque recovery after an injurious bout of ECs, and uses Affymetrix microarrays to compare the gene expression profile 48 hours after ECs to both isometrically stimulated muscles and contralateral muscles. Torque dropped by about 55% immediately after the exercise bout, and recovered to initial levels 7 days later. 36 known genes were upregulated after ECs compared to contralateral and isometrically stimulated muscles, including five muscle specific genes: muscle LIM protein (MLP), Muscle Ankyrin Repeat Proteins (MARP 1 and 2; also known as cardiac ankyrin repeat protein and Arpp/Ankrd2, respectively), Xin, and Myosin Binding Protein H. The time courses of MLP and MARP expression after the injury bout (determined by quantitative real-time polymerase chain reaction) indicate that these genes are rapidly induced, reaching a peak expression level of 6-11 times contralateral values 12-24 hours after the EC bout and returning to baseline within 72 hours. Very little gene induction was seen after either isometric activation or passive stretch, indicating that the MLP and MARP genes may play an important and specific role in the biological response of muscle to EC-induced injury. Keywords = mouse tibialis anterior eccentric isometric contraction muscle Keywords: other

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Transcriptome analysis of brain endothelial cells from adult EC-specific Glut1 knock-out mice as compared to wild type controls

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