Akt1 is involved in tubular apoptosis and inflammatory response during renal ischemia–reperfusion injury

• Published in: Molecular biology reports 2020-12, Vol.47 (12), p.9511-9520
• Main Authors: Kim, Il Young, Park, Yeon Kyeong, Song, Sang Heon, Seong, Eun Young, Lee, Dong Won, Bae, Sun Sik, Lee, Soo Bong
• Format: Article
• Language: English
• Subjects: AKT protein; AKT1 protein; AKT2 protein; Animal Anatomy; Animal Biochemistry; Animals; Apoptosis; Apoptosis - genetics; Bcl-2 protein; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Biomedical and Life Sciences; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase-3; Creatinine; Cytokines; DNA nucleotidylexotransferase; Epithelial Cells - metabolism; Epithelial Cells - pathology; Gene Expression Regulation; Histology; IL-1β; Inflammation; Interleukin 6; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Ischemia; Kidney Tubules - metabolism; Kidney Tubules - pathology; Kidneys; Life Sciences; Macrophages; Macrophages - metabolism; Macrophages - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphology; Nephrectomy; Nephrectomy - methods; Original Article; Proto-Oncogene Proteins c-akt - deficiency; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Reperfusion; Reperfusion Injury - genetics; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Signal Transduction; Therapeutic targets; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-020-06021-1

Renal ischemia–reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI). Although Akt is involved in renal IRI, it is unclear as to which Akt isoform plays an important role in renal IRI. In this study, we investigated the role of Akt1 in renal IRI. We subjected the C57BL/6 male mice to unilateral IRI with contralateral nephrectomy. Two days after IRI, IRI-kidneys were harvested. The mice were divided into four groups: wild type (WT) IRI, Akt1 −/− IRI, WT sham, and Akt1 −/− sham. We found that Akt1, not Akt2 or Akt3, was markedly activated in WT IRI than in WT sham mice. The histologic damage score and serum creatinine level significantly increased in WT IRI mice, the increase being the highest in Akt1 −/− IRI mice. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells and expression of cleaved caspase-3/Bax were higher in Akt1 −/− IRI mice than in WT IRI mice. The expression of Bcl-2 was lower in Akt1 −/− IRI mice than in WT IRI mice. The expression of tumor necrosis factor-α/interleukin-6/interleukin-1β and number of F4/80-positive macrophages were markedly higher in Akt1 −/− IRI than in WT IRI mice. The expression of phosphorylated nuclear factor-κB p65 was also higher in Akt1 −/− IRI mice than in WT IRI mice. Our results show that Akt1 deletion exacerbates kidney damage as it increases tubular apoptosis and inflammatory response during renal IRI. Akt1 could be a potential therapeutic target for developing treatments against IRI-induced AKI.