RNA-Seq identifies condition-specific biological signatures of ischemia-reperfusion injury in the human kidney

• Published in: BMC nephrology Vol. 21; no. Suppl 1; pp. 398 - 12
• Main Authors: Park, Meeyoung, Kwon, Chae Hwa, Ha, Hong Koo, Han, Miyeun, Song, Sang Heon
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 25.09.2020; BioMed Central; BMC
• Subjects: Acute kidney injury; AKT protein; Apoptosis; Cell migration; Clustering analysis; Complications and side effects; Creatinine; Death receptors; Development and progression; End-stage renal disease; Fibrosis; Gene expression; Genetic aspects; Immune response; Inflammasomes; Ischemia; Ischemia-reperfusion injury; Kidney diseases; Kidney failure; Kidney research; Medical prognosis; Metabolic pathways; Nephrology; Pathway analysis; Renal failure; Renal replacement therapy; Reperfusion; Reperfusion injury; Ribonucleic acid; RNA; RNA sequencing; Software; South Korea; United States > US; Pathway analysis; RNA-sequencing; Clustering analysis; Ischemia-reperfusion injury; Acute kidney injury
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-020-02025-y

Acute kidney injury (AKI) is defined as a sudden event of kidney failure or kidney damage within a short period. Ischemia-reperfusion injury (IRI) is a critical factor associated with severe AKI and end-stage kidney disease (ESKD). However, the biological mechanisms underlying ischemia and reperfusion are incompletely understood, owing to the complexity of these pathophysiological processes. We aimed to investigate the key biological pathways individually affected by ischemia and reperfusion at the transcriptome level. We analyzed the steady-state gene expression pattern of human kidney tissues from normal (pre-ischemia), ischemia, and reperfusion conditions using RNA-sequencing. Conventional differential expression and self-organizing map (SOM) clustering analyses followed by pathway analysis were performed. Differential expression analysis revealed the metabolic pathways dysregulated in ischemia. Cellular assembly, development and migration, and immune response-related pathways were dysregulated in reperfusion. SOM clustering analysis highlighted the ischemia-mediated significant dysregulation in metabolism, apoptosis, and fibrosis-related pathways, while cell growth, migration, and immune response-related pathways were highly dysregulated by reperfusion after ischemia. The expression of pro-apoptotic genes and death receptors was downregulated during ischemia, indicating the existence of a protective mechanism against ischemic injury. Reperfusion induced alterations in the expression of the genes associated with immune response such as inflammasome and antigen representing genes. Further, the genes related to cell growth and migration, such as AKT, KRAS, and those related to Rho signaling, were downregulated, suggestive of injury responses during reperfusion. Semaphorin 4D and plexin B1 levels were also downregulated. We show that specific biological pathways were distinctively involved in ischemia and reperfusion during IRI, indicating that condition-specific therapeutic strategies may be imperative to prevent severe kidney damage after IRI in the clinical setting.