Oligosaccharides Ameliorate Acute Kidney Injury by Alleviating Cluster of Differentiation 44-Mediated Immune Responses in Renal Tubular Cells.

Tso-Hsiao Chen,Chung-Te Liu,Yuh-Mou Sue,Chung-Yi Cheng,Cheng-Hsien Chen,Nai-Jen Huang

doi:10.3390/nu14040760

Abstract

Acute kidney injury (AKI) is a sudden episode of kidney damage that commonly occurs in patients admitted to hospitals. To date, no ideal treatment has been developed to reduce AKI severity. Oligo-fucoidan (FC) interferes with renal tubular cell surface protein cluster of differentiation 44 (CD44) to prevent renal interstitial fibrosis; however, the influence of oligosaccharides on AKI remains unknown. In this study, FC, galacto-oligosaccharide (GOS), and fructo-oligosaccharide (FOS) were selected to investigate the influence of oligosaccharides on AKI. All three oligosaccharides have been proven to be partially absorbed by the intestine. We found that the oligosaccharides dose-dependently reduced CD44 antigenicity and suppressed the hypoxia-induced expression of CD44, phospho-JNK, MCP-1, IL-1β, and TNF-α in NRK-52E renal tubular cells. Meanwhile, CD44 siRNA transfection and JNK inhibitor SP600125 reduced the hypoxia-induced expression of phospho-JNK and cytokines. The ligand of CD44, hyaluronan, counteracted the influence of oligosaccharides on CD44 and phospho-JNK. At 2 days post-surgery for ischemia–reperfusion injury, oligosaccharides reduced kidney inflammation, serum creatine, MCP-1, IL-1β, and TNF-α in AKI mice. At 7 days post-surgery, kidney recovery was promoted. These results indicate that FC, GOS, and FOS inhibit the hypoxia-induced CD44/JNK cascade and cytokines in renal tubular cells, thereby ameliorating AKI and kidney inflammation in AKI mice. Therefore, oligosaccharide supplementation is a potential healthcare strategy for patients with AKI.

Highlights

Acute kidney injury (AKI) is characterized by a sudden decrease in glomerular filtration rate and a consequent increase in serum creatinine
Hypoxia upregulated the levels of phosphorylated Jun NH2terminal kinase (JNK), monocyte chemoattractant protein-1 (MCP-1), IL-1β, and tumor necrosis factor-α (TNF-α) but not in the cells treated with oligosaccharides (Figure 1B,C)
Hypoxia induced the expression of MCP-1, IL-1α, and TNF-α in NRK-52E cells, which were inhibited by JNK inhibitor SP600125

Summary

Introduction

Acute kidney injury (AKI) is characterized by a sudden decrease in glomerular filtration rate and a consequent increase in serum creatinine. This damage is common in patients admitted to hospitals and intensive care units, especially the elderly. Severe AKI places discharged patients at risk of adverse events, such as chronic kidney disease, cardiovascular events, cancer, and infections [2]. AKI has a rapid development, and no effective treatment is available to avoid or reduce its severity. Intake of specific nutrients can reduce renal tubular injury in AKI [3]. Studying the influence of specific nutrition on AKI will aid in ameliorating AKI and accompanying risks faced by discharged patients

Methods

Results

Conclusion