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Neutrophilic inflammation is essential for defending against invading pathogens, but can also be detrimental in many clinical settings. The hematopoietic-specific small Rho-GTPase Rac2 regulates multiple pathways that are essential for neutrophil activation, including adhesion, migration, degranulation and production of reactive oxygen species. This study tested the hypothesis that partially suppressing rac2 in zebrafish neutrophils by using a microRNA (miRNA) would inhibit neutrophil migration and activation, which would reduce the immunological damage caused by systemic inflammation. We have generated a transgenic zebrafish line that overexpresses microRNA-722 (miR-722) in neutrophils. Neutrophil motility and chemotaxis to tissue injury or infection are significantly reduced in this line. miR-722 downregulates the transcript level of rac2 through binding to seed-matching sequence in the rac2 3'UTR. Furthermore, miR-722-overexpressing larvae display improved outcomes in both sterile and bacterial systemic models, which correlates with a robust upregulation of the anti-inflammatory cytokines in the whole larvae and isolated neutrophils. Finally, an miR-722 mimic protects zebrafish from lethal lipopolysaccharide challenge. Together, these results provide evidence for and the mechanism of an anti-inflammatory miRNA that restrains detrimental systemic inflammation.
Pubmed ID: 28954734 RIS Download
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsA research program of the NIA which focuses on neuroscience, aging biology, and translational gerontology. The central focus of the program's research is understanding age-related changes in physiology and the ability to adapt to environmental stress, and using that understanding to develop insight about the pathophysiology of age-related diseases. The IRP webpage provides access to other NIH resources such as the Biological Biochemical Image Database, the Bioinformatics Portal, and the Baltimore Longitudinal Study of Aging.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsCentral online repository for microRNA nomenclature, sequence data, annotation and target prediction.Collection of published miRNA sequences and annotation.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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