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CID16020046, a GPR55 antagonist, attenuates sepsis‑induced acute kidney injury

  • Authors:
    • Rongxin Chen
    • Hailin Xu
    • Zebin Guo
    • Peng Zhang
    • Jianxia Chen
    • Zheng Chen
  • View Affiliations / Copyright

    Affiliations: Organ Transplant Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 511447, P.R. China, Department of Intensive Care Unit, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 511447, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 155
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    Published online on: March 3, 2022
       https://doi.org/10.3892/mmr.2022.12671
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Abstract

Acute kidney injury (AKI) is the most common and serious complication of sepsis, and it is also the main cause of mortality in patients with sepsis. The G protein‑coupled receptor 55 (GPR55) inhibitor CID16020046 was found to suppress the inflammatory response in sepsis models in mice. The aim of the present study was to investigate the effect of CID16020046 on AKI in sepsis mouse models and elucidate the possible underlying mechanisms. A sepsis model in mice was established by cecal ligation/perforation (CLP). The expression levels of GPR55 in the serum of patients with sepsis and the renal tissues of septic mice were determined via reverse transcription‑quantitative PCR and western blot analyses, respectively. The pathological injury of renal tissue was evaluated using H&E and periodic acid‑Schiff staining. ELISA was performed to detect the levels of renal injury‑related factors, including blood urea nitrogen (BUN), creatinine (Cre), kidney injury molecule 1 (KIM1) and neutrophil gelatinase‑associated lipocalin (NGAL) in septic mice. Moreover, the levels of pro‑inflammatory cytokines (TNF‑α, IL‑6 and IL‑1β) were detected via ELISA and western blotting. Apoptosis was determined using TUNEL staining and western blotting. The expression levels of Rho‑associated protein kinase (ROCK) pathway‑related proteins (Ras homolog family member A, ROCK1 and ROCK2) was measured via western blotting. Finally, H&E staining was used to evaluate the effect of CID16020046 on various organs in mice. Compared with the control subjects, the expression level of GPR55 in the serum of patients with sepsis was significantly increased. Compared with the sham group, CID16020046 (20 mg/kg) significantly decreased the levels of BUN and Cre in the serum, as well as the contents of KIM1 and NGAL in the urine. Furthermore, CID16020046 significantly decreased the contents of TNF‑α, IL‑6 and IL‑1β in the serum and renal tissue of septic mice, and reduced cell apoptosis. In addition, CID16020046 effectively suppressed the expression levels of ROCK pathway‑related proteins, and H&E staining revealed that CID16020046 (20 mg/kg) had no toxic effect on the heart, liver, spleen or lung in normal mice. In conclusion, CID16020046 may prove useful for the development of drugs for the treatment of sepsis‑induced AKI.
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Copy and paste a formatted citation
Spandidos Publications style
Chen R, Xu H, Guo Z, Zhang P, Chen J and Chen Z: CID16020046, a GPR55 antagonist, attenuates sepsis‑induced acute kidney injury. Mol Med Rep 25: 155, 2022.
APA
Chen, R., Xu, H., Guo, Z., Zhang, P., Chen, J., & Chen, Z. (2022). CID16020046, a GPR55 antagonist, attenuates sepsis‑induced acute kidney injury. Molecular Medicine Reports, 25, 155. https://doi.org/10.3892/mmr.2022.12671
MLA
Chen, R., Xu, H., Guo, Z., Zhang, P., Chen, J., Chen, Z."CID16020046, a GPR55 antagonist, attenuates sepsis‑induced acute kidney injury". Molecular Medicine Reports 25.5 (2022): 155.
Chicago
Chen, R., Xu, H., Guo, Z., Zhang, P., Chen, J., Chen, Z."CID16020046, a GPR55 antagonist, attenuates sepsis‑induced acute kidney injury". Molecular Medicine Reports 25, no. 5 (2022): 155. https://doi.org/10.3892/mmr.2022.12671
Copy and paste a formatted citation
x
Spandidos Publications style
Chen R, Xu H, Guo Z, Zhang P, Chen J and Chen Z: CID16020046, a GPR55 antagonist, attenuates sepsis‑induced acute kidney injury. Mol Med Rep 25: 155, 2022.
APA
Chen, R., Xu, H., Guo, Z., Zhang, P., Chen, J., & Chen, Z. (2022). CID16020046, a GPR55 antagonist, attenuates sepsis‑induced acute kidney injury. Molecular Medicine Reports, 25, 155. https://doi.org/10.3892/mmr.2022.12671
MLA
Chen, R., Xu, H., Guo, Z., Zhang, P., Chen, J., Chen, Z."CID16020046, a GPR55 antagonist, attenuates sepsis‑induced acute kidney injury". Molecular Medicine Reports 25.5 (2022): 155.
Chicago
Chen, R., Xu, H., Guo, Z., Zhang, P., Chen, J., Chen, Z."CID16020046, a GPR55 antagonist, attenuates sepsis‑induced acute kidney injury". Molecular Medicine Reports 25, no. 5 (2022): 155. https://doi.org/10.3892/mmr.2022.12671
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