Dataset Information

Honokiol alleviates sepsis-induced acute kidney injury in mice by targeting the miR-218-5p/heme oxygenase-1 signaling pathway.

ABSTRACT:

Background

Honokiol is a low-molecular-weight natural product and has been reported to exhibit anti-inflammatory activity.

Objectives

Our study aimed to investigate the influence of honokiol on sepsis-induced acute kidney injury (AKI) in a mouse model.

Material and methods

A cecal ligation and puncture (CLP) surgical operation was performed to establish a sepsis-induced acute kidney injury model in mice. Renal histomorphological analysis was performed with periodic acid-Schiff (PAS) staining. The levels of inflammatory markers in serum were measured by ELISA assay. The mRNA and protein levels were assayed by RT-qPCR and western blotting, respectively. Annexin V-FITC/PI staining was used to evaluate glomerular mesangial cell (GMC) apoptosis.

Results

The results revealed that honokiol significantly increased the survival rate in mice undergoing a CLP operation. Inflammatory cytokines, such as TNF-α, IL-6 and IL-1β, were significantly inhibited in honokiol-treated septic mice compared with the CLP group. In addition, honokiol showed the ability to reverse CLP-induced AKI in septic mice. Furthermore, heme oxygenase-1 (HO-1) expression levels were significantly up-regulated and miR-218-5p was markedly down-regulated in honokiol-treated septic mice as compared to CLP-operated mice. Bioinformatics and experimental measurements showed that HO-1 was a direct target of miR-218-5p. In vitro experiments showed that both honokiol and miR-218-5p inhibitors blocked lipopolysaccharide (LPS)-induced cell growth inhibition and GMC apoptosis by increasing the expression of HO-1.

Conclusions

Honokiol ameliorated AKI in septic mice and LPS-induced GMC dysfunction, and the underlying mechanism was mediated, at least partially, through the regulation of miR-218-5p/HO-1 signaling.

SUBMITTER: Zhang T

PROVIDER: S-EPMC6387556 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Honokiol alleviates sepsis-induced acute kidney injury in mice by targeting the miR-218-5p/heme oxygenase-1 signaling pathway.

Zhang Tao T Xiang Lei L

Cellular & molecular biology letters 20190222

<h4>Background</h4>Honokiol is a low-molecular-weight natural product and has been reported to exhibit anti-inflammatory activity.<h4>Objectives</h4>Our study aimed to investigate the influence of honokiol on sepsis-induced acute kidney injury (AKI) in a mouse model.<h4>Material and methods</h4>A cecal ligation and puncture (CLP) surgical operation was performed to establish a sepsis-induced acute kidney injury model in mice. Renal histomorphological analysis was performed with periodic acid-Sch ...[more]

PMID: 30833971

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Project description:Background Sepsis patients suffer from severe inflammation and poor prognosis. Oxidative stress and local inflammation that results from sepsis can trigger organ injury, including acute kidney injury (AKI). Previous studies have shown that heme oxygenase-1 (HO-1) is overexpressed in proximal tubular cells under oxidative stress and has significant cytoprotective and anti-inflammatory effects. Heme-induced inflammation in sepsis is antagonized by increased tissue expression of heme oxygenase-1 (HO-1), which impacts on AKI development. The investigators observed intrarenal HO-1 expression and corresponding potential increases in plasma and urinary HO-1 protein concentrations in four different AKI models. Since serum levels of HO-1 reflect HO-1 expression, we aimed to investigate whether serum HO-1 could predict the development of AKI in sepsis patient. Methods A total of 83 sepsis patients were enrolled in this study including septic patients with AKI and sepsis patients without AKI. According to the definition of septic shock and the global kidney diagnostic criteria described in the Kidney Disease: Improving Global Outcomes (KDIGO), patients were allocated to the sepsis and septic shock groups with and without AKI, respectively. The serum levels of HO-1 were measured by enzyme-linked immunosorbent assays (ELISA). Statistical analyses were performed using SPSS software. Results There were statistically significant differences between septic patients with AKI and sepsis patients without AKI in terms of Sequential Organ Failure Assessment (SOFA) score, hospitalization time, and laboratory indicators including serum HO-1, creatine kinase MB (CK-MB), troponin I (TnI), urea, myoglobin (MYO), serum creatinine (Scr), procalcitonin, and activated partial thromboplastin time. Serum levels of alkaline phosphatase (ALP), urea, MYO, Scr, procalcitonin, activated partial thromboplastin time, and prothrombin time exhibited significant differences among the four groups. The concentration of serum HO-1 was higher in sepsis-induced AKI compared with sepsis patients without AKI. Serum HO-1 levels were increased in patients with sepsis shock-induced AKI. The area under the receiver operating characteristic (ROC) curve for serum HO-1 combined with Scr was 0.885 [95% confidence interval (CI): 0.761–1.000]. Conclusions Serum HO-1 is positively correlated with sepsis-induced AKI. These findings suggest that measurement of serum HO-1 may play a diagnostic and prediction role in sepsis-induced AKI.

Dataset Information

Honokiol alleviates sepsis-induced acute kidney injury in mice by targeting the miR-218-5p/heme oxygenase-1 signaling pathway.

Background

Objectives

Material and methods

Results

Conclusions

Publications

Honokiol alleviates sepsis-induced acute kidney injury in mice by targeting the miR-218-5p/heme oxygenase-1 signaling pathway.

Similar Datasets

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