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

Meeyoung Park,Hong Koo Ha,Chae Hwa Kwon,Miyeun Han,Sang Heon Song

doi:10.1186/s12882-020-02025-y

Meeyoung Park, Hong Koo Ha + Show 3 more

Open Access

https://doi.org/10.1186/s12882-020-02025-y

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Journal: BMC Nephrology	Publication Date: Sep 1, 2020
Citations: 15	License type: open-access

Affiliation: Pusan National University Hospital

Abstract

BackgroundAcute 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.ResultsWe 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.ConclusionsWe 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.

Highlights

Acute kidney injury (AKI) is defined as a sudden event of kidney failure or kidney damage within a short period
According to a recent meta-analysis of 154 studies based on the strict definition by Kidney Disease: Improving Global Outcomes (KDIGO), 23% AKI incidence occur during hospitalization and mortality is reported in approximately 50–80% patients with severe AKI [4]
Interventions such as continuous renal replacement therapy have been increasingly adopted as a treatment strategy in patients with severe AKI, which has evolved into a socioeconomic burden [5]

Summary

Introduction

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). According to a recent meta-analysis of 154 studies based on the strict definition by Kidney Disease: Improving Global Outcomes (KDIGO), 23% AKI incidence occur during hospitalization and mortality is reported in approximately 50–80% patients with severe AKI [4]. Interventions such as continuous renal replacement therapy have been increasingly adopted as a treatment strategy in patients with severe AKI, which has evolved into a socioeconomic burden [5].

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