대한신장학회

논문분류	춘계학술대회 초록집
제목	Identification of key genes and biological pathways associated with ischemia-reperfusion injury in the human kidney using RNA-seq
저자	Meeyoung Park, Chae Wha Kwon, Miyeun Han, Sang Heon Song
출판정보	2019; 2019(1):
키워드	acute kidney injury \| ischemia reperfusion injury \| RAN-seq \| pathway analysis
초록	Ischemia-reperfusion injury (IRI) is a very complex pathologic process. We aim to identify the key dysregulated genes and canonical pathways in IRI in human kidney tissues using RNA-sequencing (RNA-seq). Five male patients scheduled for total nephrectomy due to renal cell carcinoma or transitional cell carcinoma were enrolled. The average age of patients was 64.8 years. Kidney functions before surgery were intact (mean creatinine: 0.89 mg/dL, mean estimated glomerular filtration rate: 88.1 mL/min, mean hemoglobin: 14.2 g/dl). Kidney tissues were obtained by gun biopsy pre-hypoxia, after 15 minutes of hypoxia, and after 10 minutes of reperfusion. To identify biological mechanisms affected by IRI at the transcriptomic level, we analyzed steady‐state gene expression using RNA‐seq. The significantly differentially expressed genes (DEGs) between the groups (pre-ischemia vs. ischemia, ischemia vs. reperfusion, pre-ischemia vs. reperfusion) were identified (adjusted p-value < 0.1). DEGs were analyzed to discover the significantly enriched biological pathways during ischemia and reperfusion (p-value < 0.05). We identified significantly enriched canonical pathways that may be related to the IRI. DEGs affected by ischemia (pre-ischemia vs. ischemia) were related to a well-known hypoxic response such as phosphatidylcholine metabolism, and aryl hydrocarbon receptor, heat shock proteins (HSPs) and JAK/STAT signaling pathway. DEGs affected by reperfusion (ischemia vs. reperfusion) were enriched in pathways associated with sphingolipids metabolism, and oxidative stress responses. However, DEGs affected by both ischemia and reperfusion (pre-ischemia vs. reperfusion) were significantly enriched in inflammatory response including MAPK signaling pathway and pathway related to signaling and production of cytokines such as IL-1, IL-8, IL-15, and IL-17. We showed that different biological pathways are involved in IRI depending on the damage processes (ischemia only, reperfusion only, or both) in the human kidney. Therefore, we suggest that process-specific pathologic approaches might be needed to effectively prevent severe damage after ischemia-reperfusion.
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