DNA-Aptamer Raised against Receptor for Advanced Glycation End Products Improves Survival Rate in Septic Mice
| Autor: | Minoru Yagi, Tatsuyuki Kakuma, Yoshiaki Tanaka, Sho-ichi Yamagishi, Jun Akiba, Takanori Matsui, Naoki Hashizume, Yoshinori Koga, Yuri Nishino, Yuichiro Higashimoto, Ami Sotokawauchi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Glycation End Products
Advanced Lipopolysaccharides Male Aging Article Subject Lipopolysaccharide endocrine system diseases Pharmacology medicine.disease_cause HMGB1 Biochemistry RAGE (receptor) Diabetic nephropathy Sepsis Mice chemistry.chemical_compound Glycation medicine Animals HMGB1 Protein Receptor Mice Inbred BALB C biology QH573-671 business.industry NF-kappa B Cell Biology General Medicine Acute Kidney Injury Aptamers Nucleotide Liver Failure Acute medicine.disease Survival Rate Oxidative Stress chemistry biology.protein Acidosis business Cytology Oxidative stress Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2021 (2021) Oxidative Medicine and Cellular Longevity |
| ISSN: | 1942-0994 1942-0900 |
| Popis: | Despite remarkable scientific advances in the understanding of molecular mechanisms for sepsis, therapeutic options are far from satisfactory. High mobility group box 1 (HMGB1), one of the ligands of receptor for advanced glycation end products (RAGE), is a late mediator of lethality in septic mice. We have recently found that the DNA-aptamer raised against RAGE (RAGE-aptamer) significantly blocks experimental diabetic nephropathy and melanoma growth and metastasis. We examined the effects of RAGE-aptamer on sepsis score, survival rate, and inflammatory and oxidative stress responses in serum, peripheral monocytes, kidneys and livers of lipopolysaccharide- (LPS-) injected mice, and on LPS-exposed THP-1 cells. RAGE-aptamer inhibited the binding of HMGB1 to RAGE in vitro. RAGE-aptamer significantly ( P = 0.002 ) improved sepsis score at 8 hours after LPS injection and survival rate at 24 hours ( P < 0.01 , 70%) in septic mice compared with LPS+vehicle- or LPS+control-aptamer-treated mice. RAGE-aptamer treatment significantly decreased expression of p-NF-κB p65, an active form of redox-sensitive transcriptional factor, NF-κB and gene or protein expression of TNF-α, IL-1β, IL-6, and HMGB1 in serum, peripheral monocytes, and kidneys of septic mice in association with the reduction of oxidative stress and improvement of metabolic acidosis, renal and liver damage. LPS-induced oxidative stress, inflammatory reactions, and growth suppression in THP-1 cells were significantly blocked by RAGE-aptamer. Our present study suggests that RAGE-aptamer could attenuate multiple organ damage in LPS-injected septic mice partly by inhibiting the inflammatory reactions via suppression of HMGB1-RAGE interaction. |
| Databáze: | OpenAIRE |
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