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KLF14和SREBF-1结合位点与代谢综合征中孤儿受体启动子的关联

KLF14 and SREBF-1 Binding Site Associations with Orphan Receptor Promoters in Metabolic Syndrome.

作者信息

Garcia-Coste Julio Jesús, Villafaña-Rauda Santiago, Aguayo-Cerón Karla Aidee, Vargas-De-León Cruz, Romero-Nava Rodrigo

机构信息

Laboratorio de Investigación en Genética de Enfermedades Metabólicas, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico.

Laboratorio de Modelación Bioestadística para la Salud, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico.

出版信息

Int J Mol Sci. 2025 Mar 21;26(7):2849. doi: 10.3390/ijms26072849.

Abstract

This study investigated the relationship between the transcription factors (TFs) KLF14 and SREBF-1 and orphan receptors (ORs) in the context of metabolic syndrome (MetS). A detailed bioinformatics analysis identified a significant association between the presence of binding sites (BS) for these TFs in the promoters of ORs genes and the total number of BS in the distal region. The results suggest that KLF14 and SREBF-1 can regulate the expression of some of these genes and, in turn, can modulate the development of MetS. Although a stronger association was observed with KLF14, both factors showed a significant contribution. Additionally, the sequence similarity of KLF14 also contributed to the quantity of BS in the gene's distal region (DR). The statistical models used, such as Poisson and negative binomial regression, confirmed these associations and allowed for the appropriate adjustment of overdispersion present in the data. However, no significant differences in receptor groups (orphan G Protein-Coupled Rereptors (oGPCRs) and G Protein-Coupled Receptors associated with MetS (GPCRs-MetS)) regarding their relationship with TFs were found. In conclusion, this study provides strong evidence of the importance of KLF14 and SREBF-1 in regulating orphan receptors genes and their participation in the development of metabolic syndrome.

摘要

本研究在代谢综合征(MetS)背景下,调查了转录因子(TFs)KLF14和SREBF - 1与孤儿受体(ORs)之间的关系。详细的生物信息学分析确定了这些转录因子在孤儿受体基因启动子中的结合位点(BS)的存在与远端区域中结合位点总数之间存在显著关联。结果表明,KLF14和SREBF - 1可以调节其中一些基因的表达,进而调节代谢综合征的发展。尽管观察到与KLF14的关联更强,但这两个因子均显示出显著作用。此外,KLF14的序列相似性也对基因远端区域(DR)中结合位点的数量有贡献。所使用的统计模型,如泊松回归和负二项回归,证实了这些关联,并对数据中存在的过度离散进行了适当调整。然而,未发现受体组(孤儿G蛋白偶联受体(oGPCRs)和与代谢综合征相关的G蛋白偶联受体(GPCRs - MetS))与转录因子的关系存在显著差异。总之,本研究提供了有力证据,证明KLF14和SREBF - 1在调节孤儿受体基因及其参与代谢综合征发展方面的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a2/11988724/d7c96185c733/ijms-26-02849-g0A1.jpg

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