Aquaporin 1 alleviates acute kidney injury via PI3K-mediated macrophage M2 polarization
| Autor: | Bohui Li, Xuening Dong, Kaihong Tang, Guangming Su, Yingyu Jin, Chunmei Liu, Longge Xue |
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| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Lipopolysaccharide Immunology Macrophage polarization Nitric Oxide Synthase Type II Kidney Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system medicine Animals Macrophage Rats Wistar Tissue homeostasis Pharmacology Aquaporin 1 Interleukin-6 Tumor Necrosis Factor-alpha Macrophages Acute Kidney Injury M2 Macrophage RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | Inflammation Research. 69:509-521 |
| ISSN: | 1420-908X 1023-3830 |
| DOI: | 10.1007/s00011-020-01334-0 |
| Popis: | Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with an abnormal immune response. Accumulating evidence has demonstrated that aquaporin 1 (AQP1) prevents kidney tissue injury in LPS-induced AKI by mediating immune response. However, the underlying mechanisms remain obscure. Macrophages as immune cells with multiple phenotypes are important mediators in tissue homeostasis and host defense. We propose that macrophage polarization is implicated in AQP1-mediated immune response. Herein we established sepsis-induced AKI model rats through intraperitoneal injection of LPS into Wistar rats to reveal immune mechanism of damage. We also used LPS-induced mouse RAW264.7 cells to elucidate the molecular mechanism of macropage polarization. Histopathology showed that renal tubular epithelial cells in the model group were swollen, inflammatory exudation was obvious and the inflammatory factors, interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were increased. Western blotting showed PI3K was upregulated in the model group. Serum creatinine and urea nitrogen increased after LPS injection. Renal AQP1 mRNA is downregulated and serum AQP1 protein increased first and then decreased in LPS-induced AKI rats. M2 macrophage markers (Arg-1, CD206) were increased in repair stage. In addition, treatment of murine macrophages (RAW264.7) with AQP1 siRNA resulted in decreased PI3K activation and M2 polarization, but increased IL-6 and TNF-α. Moreover, inhibiting PI3K with wortmannin imitated the results of AQP1 silencing. Macrophage M2 polarization is likely the cellular mechanism underlying the anti-AKI property of AQP1, and PI3K activation is involved in the AQP1-induced M2 phenotype switch. |
| Databáze: | OpenAIRE |
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