Dataset Information

Cross-species comparative transcriptomics examining the role of Type-2 immunity in acute colitis

ABSTRACT: Most preclinical models of IBD were developed in mice which share 85% genomic homology with humans and are genetically tractable. However, rats have historically been the model of choice for immunologic, cardiovascular, and neurologic diseases because they more closely recapitulate human physiology6. Recent work on the role of microbial dysbiosis in IBD has also shown that rat microbiota is more closely related to those of humans than mice7. Taken together, this suggests that a single preclinical model may not be optimal for delineating the molecular pathways involved in IBD pathogenesis. Previous research in rat models of IBD have focused primarily on characterization of clinical score and histopathological findings8, with a lack of systematic investigation into potential molecular pathways affected, thereby making it difficult to integrate this model with other preclinical and clinical research. In the current study, we have undertaken a systematic transcriptomic analysis of a rat model of experimental colitis along with a three-way comparison between an established mouse preclinical model and available human clinical datasets in an effort to identify conserved immunological pathways in IBD.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE245994 | GEO | 2023/11/06

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Uterine leiomyomata, or fibroids, are benign tumors of the uterine myometrium that significantly affect up to 30% of reproductive-age women. Despite being the primary cause of hysterectomy in the United States, accounting for up to 200,000 procedures annually, the etiology of leiomyoma remains largely unknown. Due to the lack of an effective medicinal therapy for these tumors, this disease continues to have a tremendous negative impact on women’s health. As a basis for understanding leiomyoma pathogenesis and identifying targets for pharmacotherapy, we conducted transcriptional profiling of leiomyoma and unaffected myometrium from humans and Eker rats, the best characterized preclinical model of leiomyoma. A global comparison of mRNA from leiomyoma versus myometrium in human and rat identified a highly significant overlap of dysregulated gene expression in leiomyoma. An unbiased pathway analysis using a method of gene set enrichment based on the Sigpathway algorithm detected the mammalian target of rapamycin (mTOR) pathway as one of the most highly upregulated pathways in both human and rat tumors. Activation of this pathway was confirmed in both human and rat leiomyomata at the protein level via Western. Inhibition of mTOR in female Eker rats with the rapamycin analog WAY-129327 for 2 weeks decreased mTOR signaling and cell proliferation in tumors, and treatment for 4 months significantly decreased tumor incidence, multiplicity and size. These results identify dysregulated mTOR signaling as a component of leiomyoma etiology across species and directly demonstrate the dependence of these tumors on mTOR signaling for growth in the Eker rat. Modulation of this pathway warrants additional investigation as a potential therapy for uterine leiomyoma. Experiment Overall Design: We analyzed 1-3 leiomyoma or normal myometrium biopsies from each 23 woman undergoing hysterectomy for the treatment of uterine fibroids. tment and compared it leiomyoma and normal myometrium from the Eker rat model of uterine fibroids (N=14-15)

Dataset Information

Cross-species comparative transcriptomics examining the role of Type-2 immunity in acute colitis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets