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Unveiling ELAVL1 as a key RNA-binding protein regulating the chemokine signaling pathway in diabetic nephropathy
Seyed Amirhossein Hosseini1,2,3, Parisa Ajorlou2,4,3, Ali Bandsariyan3
1Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Abstract:
The chemokine signaling pathway is a key factor in inflammation and the development of diabetic nephropathy (DN). The involvement of RNA-binding proteins (RBPs) in modulating this pathway is not yet fully clarified. This study aimed to examine the regulatory role of RBPs in the chemokine signaling pathway associated with DN. Using transcriptional data from the GSE142153 dataset, DEGs were identified. By intersecting DN-associated DEGs with chemokine pathway genes from the MSigDB database, 30 common genes were identified. Four hub genes were then selected through PPI network analysis. Target RBPs of these hub genes were predicted using the RNAInter database, with ELAVL1 identified as a shared regulatory RBP. The expression of ELAVL1 was further validated in the GSE142025 dataset. ELAVL1 gene expression was measured in 90 PBMC samples from three groups: T2D patients, DN patients, and healthy controls, with 30 individuals in each group. Real-time PCR results demonstrated a significant upregulation of ELAVL1 in DN patients versus T2D and control groups. This study highlights the critical role of ELAVL1 in promoting inflammation through the chemokine signaling pathway and contributing to renal injury. Thus, ELAVL1 could be considered a valuable biomarker for identifying and tracking the development of DN.
Insights
RNA-binding protein ELAVL1 is upregulated in diabetic nephropathy (DN) patients, promoting inflammation via the chemokine pathway. ELAVL1 may serve as a biomarker for DN development and progression.
Area of Science:
- Molecular Biology
- Genetics
- Immunology
Background:
- The chemokine signaling pathway is crucial in inflammation and diabetic nephropathy (DN) pathogenesis.
- The role of RNA-binding proteins (RBPs) in regulating this pathway in DN remains unclear.
Purpose of the Study:
- To investigate the regulatory function of RBPs in the chemokine signaling pathway within the context of DN.
- To identify potential RBPs involved in DN pathogenesis.
Main Methods:
- Differential gene expression analysis of transcriptomic data (GSE142153).
- Identification of common genes between DN-associated DEGs and chemokine pathway genes.
- Protein-protein interaction (PPI) network analysis to identify hub genes.
- Prediction of target RBPs using RNAInter database.
- Validation of ELAVL1 expression in an independent dataset (GSE142025) and PBMC samples via real-time PCR.
Main Results:
- Thirty common genes were identified between DN DEGs and chemokine pathway genes.
- Four hub genes were identified through PPI network analysis.
- ELAVL1 was predicted as a shared regulatory RBP for these hub genes.
- ELAVL1 expression was significantly upregulated in peripheral blood mononuclear cells (PBMCs) of DN patients compared to type 2 diabetes (T2D) patients and healthy controls.
Conclusions:
- ELAVL1 plays a critical role in promoting inflammation through the chemokine signaling pathway, contributing to renal injury in DN.
- ELAVL1 is a potential biomarker for the identification and monitoring of DN development.
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