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Kidney Week

Abstract: TH-PO465

The Deletion of Akt1 Exacerbates the Renal Fibrosis via Transforming Growth Factor β1 Induction

Session Information

  • CKD: Mechanisms - I
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Kim, Il Young, Pusan National University Yangsan Hospital, Yangsan, Korea (the Republic of)
  • Ye, Byung Min, Pusan National University Yangsan Hospital, Yangsan, Korea (the Republic of)
  • Lee, Dong Won, Pusan National University Yangsan Hospital, Yangsan, Korea (the Republic of)
  • Lee, Soo Bong, Pusan National University Yangsan Hospital, Yangsan, Korea (the Republic of)
  • Han, Miyeun, Pusan National University Hospital, Busan, Korea (the Republic of)
  • Rhee, Harin, Pusan National University Hospital, Busan, Korea (the Republic of)
  • Seong, Eun Young, Pusan National University Hospital, Busan, Korea (the Republic of)
  • Song, Sang Heon, Pusan National University Hospital, Busan, Korea (the Republic of)
Background

Renal fibrosis is the hallmark of all progressive kidney disease. However, the mechanisms of renal fibrosis are poorly understood. Previous studies have found the increased Akt activity in experimental renal fibrosis. In this study, we investigated the role of Akt1, one of the three Akt isoforms, in renal fibrosis using the murine model of unilateral ureteral obstruction (UUO).

Methods

In vivo, we subjected the wild type and Akt1−/− mice to UUO. In vitro, gene silencing of Akt1 was achieved using the short hairpin RNA delivered by the lentiviral vector in immortalized human proximal tubular cells (HK2 cells) and rat kidney fibroblasts (NRK-49F cells). Western blot and immunohistochemical stain were used to investigate the mode of action of Akt1 in vivo and in vitro.

Results

In immunohistochemical stain, the expression of Akt1 was significantly higher in obstructed kidneys of wild type mice compared with control sham kidneys and increased gradually as UUO progressed. The fibronectin, type I collagen, and heat shock protein 47 (HSP47) were markedly more expressed in obstructed kidneys of Akt1−/− mice than in those of the wild type mice. Transforming growth factor β1 (TGFβ1) was highly induced within 1 day of UUO in obstructed kidneys of Akt1−/− mice and the expression of TGFβ1 was significantly higher in the Akt1−/− mice than in the wild type mice as UUO progressed. Western blot showed that silencing of Akt1 increased the expression of TGFβ1, which was enhanced by angiotensin II stimulation in HK2 cells, but not in NRK-49F cells. Immunohistochemical stain demonstrated that the expression of cleaved caspase-3 in renal tubules was significantly higher in the Akt1−/− mice than in the wild type mice. Western blot showed that silencing of Akt1 increased the expression of cleaved caspase-3 in HK2 cells, but not in NRK-49F cells.

Conclusion

TGFβ1 was induced in vivo and in vitro by the genetic deletion of Akt1. Our findings suggest that deletion of Akt1 might contribute to renal fibrosis and tubular apoptosis via TGFβ1 induction.