Abstract: TH-PO117
Multi-Omics Conjoint Analysis Identified pglyrp1 as a Potential Biomarker and Target for Sepsis-Induced AKI
Session Information
- AKI: Mechanisms - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- You, Ruilian, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Xu, Lubin, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Xu, Jiatong, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Ma, Yixin, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Lin, Jianfeng, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Zhu, Huadong, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
- Chen, Limeng, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
Background
Sepsis-induced acute kidney injury (SI-AKI) is a frequent complication of critical patients leading to high morbidity and mortality without a satisfactory prognosis. Further studies are needed to unveil the SI-AKI mechanisms for detecting new biomarkers and treatment targets.
Methods
We conducted the phenome-wide Mendelian randomization (MR-PheWAS) using the 2116 instruments for 1699 proteins from the open protein quantitative trait loci (pQTLs) data published by the Jie Zheng et al. and the genome-wide association studies (GWAS) of the acute kidney failure including 456348 European. Adjusted P < 3X10E-5 was considered significant and P < 0.05 was considered suggestive of an association. We selected the expression profile GSE125276 from the Gene Expression Omnibus (GEO) database to analyze the differentially expressed genes (DEGs) of the SI-AKI. Animal model of SI-AKI was established with lipopolysaccharides (LPS). Common gene identified based on the genome and the transcriptome was validated by the quantitative real-time PCR (qRT-PCR) and western blot.
Results
A total of 61 proteins were considered suggestive of an association by the MR-PheWAS, including 34 protective genes and 27 risk proteins. The 316 DEGs were identified from the GSE125276. Csf2rb, pglyrp1, and slurp1 were common genes of the multi-omics analysis. Pglyrp1 was included in the top hub module extracted from the molecular complex detection (MCODE). The RNA and protein expression levels of the pglyrp1 are all significantly elevated in the nephron tissue of the SI-AKI mice compared to control group.
Conclusion
Our study first combined the MR-PheWAS method using genome data and expression data in SI-AKI, validated that pglyrp1 upregulated as a potential casual risk molecular of the SI-AKI.