Genomics

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Substance P receptor-dependent genes and TFs


ABSTRACT: Tachykinins (TKs) are a family of peptides involved in the peripheral and central regulation of urinary functions through the stimulation of neurokinin (NK) NK1, NK2 and NK3 receptors. Recent evidence indicates that NK1 receptors are required in antigen-induced cystitis. Therefore, determining the regulatory network downstream NK1 receptor activation is a key step toward understanding the role of TKs in inflammation. For this purpose, we used a Transcriptional Regulatory Network Analysis (TRNA) to identify biologically relevant transcriptional regulatory elements (TRE) that underline the NK1-dependent gene expression in bladder responses to inflammation. Gene expression analysis was obtained using the urinary bladder isolated from WT and NK1-R-/- mice that were stimulated with intravesical instillation of saline or antigen challenge (in sensitized mice) in order to promote cystitis. Based on cDNA array results, we selected a cluster of genes that was dependent on NK1 receptors for their up-regulation in response to inflammation. Next, we used PAINT database to retrieve upstream promoter sequences for those NK1-R-dependent genes and to identify TREs on those promoters. Finally, TREs were enriched statistically by selecting only those that were significantly expressed and a regulatory network downstream of NK1 receptor activation was determined. This work indicates an overriding participation of NK1 receptors in bladder inflammation, provides a working model for the involvement of transcription regulators such as AP1, NF-kB, and Nkx-2.5, and evokes testable hypotheses regarding the regulatory network downstream of NK1 receptor activation. Keywords: URINARY BLADDER INFLAMMATION

ORGANISM(S): Mus musculus

PROVIDER: GSE2821 | GEO | 2005/06/17

SECONDARY ACCESSION(S): PRJNA92377

REPOSITORIES: GEO

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