MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN
| Autor: | Yali Wang, Xudong Wang, Jianping Yang, Mingjian Kong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male PTEN Biophysics H&E stain Down-Regulation Cell Death & Injury Apoptosis Kidney Biochemistry Molecular Bases of Health & Disease Blood Urea Nitrogen Cell Line Sepsis sepsis Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine In vivo medicine Animals Humans miR-22-3p nflammation Molecular Biology Research Articles TUNEL assay biology business.industry Acute kidney injury PTEN Phosphohydrolase Cell Biology Acute Kidney Injury medicine.disease Disease Models Animal MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Creatinine Cell Cycle Growth & Proliferation Cancer research biology.protein Cytokines business |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 0144-8463 |
| Popis: | Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury. Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p. Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response. Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN. |
| Databáze: | OpenAIRE |
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