Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse aorta smooth muscle cells reveals they differentiate into lymphoid tissue organizers upon combined TNFR1/LTBR NF-kB signaling

ABSTRACT: Cultured mouse aorta endothelial cells (from 8-12 weeks old C57BL/6J mice, passage 2-3) were exposed to phosphate buffered saline (control) or a combination of TNFalpha plus agonistic alpha-LTÃ?R antibody for 24 hours as described in LÃ¶tzer et al. 2009. Arterioscler. Thromb. Vasc. Biol., in press. Total RNA was extracted and microarrays were prepared. Experiment Overall Design: Mouse aorta endothelial cells in tissue culture were stimulated with agonists and subsequently microarray, RT-PCR, and protein assays / analyses were performed.

ORGANISM(S): Mus musculus

SUBMITTER: Andreas Johann Richard Habenicht

PROVIDER: E-GEOD-19139 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Mouse aorta smooth muscle cells (SMCs) express TNF receptor superfamily member 1A (TNFR1) and lymphotoxin Ã receptor (LTÃR). Circumstantial evidence has linked the SMC LTÃR to tertiary lymphoid organogenesis in diseased aortae of hyperlipidemic mice. Here, we explored potential roles of TNFR1 and LTÃR activation in cultured SMCs. TNFR1 signaling by TNF activated the classical RelA NF-ÎºB pathway, whereas LTÃR signaling by agonistic anti LTÃR antibody activated both the classical RelA and alternative RelB NF-ÎºB pathways. Addition of both agonists synergized to enhance p100 inhibitor processing to the p52 subunit of NF-ÎºB and promoted its nuclear translocation suggesting RelA-RelB cross-talk in transcription regulation. Correspondingly, microarrays showed that simultaneous TNFR1 and LTÃR activation when compared to activation of single receptors was followed by markedly elevated levels of mRNAs encoding leukocyte homeostatic chemokines CCL2, CCL5, CXCL1, and CX3CL1. Furthermore, SMCs acquired prototypical features of mesenchymal cells known as lymphoid tissue organizers (LTOs), which control tertiary lymphoid organogenesis in autoimmune diseases, through hyperinduction of CCL7, CCL9, CXCL13, CCL19, CXCL16, VCAM-1, and ICAM-1. Experiments with ltbr-/- SMCs suggested that the LTÃR-RelB activation component of NF-ÎºB signaling was obligatory to generate the LTO phenotype. TNFR1-LTÃR crosstalk also resulted in augmented synthesis and prolonged secretion of lymphorganogenic chemokine proteins into the culture medium. Thus, combined TNFR1-LTÃR signaling triggers SMC transdifferentiation into a phenotype that strikingly resembles LTOs. LTO-like SMCs may adopt a thus far unrecognized role in diseased arteries, i.e. to coordinate tertiary lymphoid organogenesis in atherosclerosis, aortic aneurysm, and transplant vasculopathy. Experiment Overall Design: Smooth muscle cells in tissue culture were stimulated with agonists and subsequently microarray, RT-PCR, and protein assays / analyses were performed

Dataset Information

Transcription profiling of mouse aorta smooth muscle cells reveals they differentiate into lymphoid tissue organizers upon combined TNFR1/LTBR NF-kB signaling

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets