Pharmacological Inhibition of PTEN Aggravates Acute Kidney Injury

  • Sci Rep. 2017 Aug 25;7(1):9503. doi: 10.1038/s41598-017-10336-8.
Jun Zhou  1  2 ,  Li Jia  1 ,  Zhaoyong Hu  1 ,  Yanlin Wang  3  4
Affiliations
  • 1. Selzman Institute for Kidney Health and Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
  • 2. Department of Anesthesiology, Affiliated Foshan Hospital of Sun Yat-Sen University, Foshan, China.
  • 3. Selzman Institute for Kidney Health and Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. [email protected].
  • 4. Center for Translational Research on Inflammatory Diseases (CTRID) and Renal Section, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA. [email protected].
PMID: 28842716 DOI: 10.1038/s41598-017-10336-8
Abstract

Renal ischemia/reperfusion is a major cause of acute kidney injury. However, the pathogenic mechanisms underlying renal ischemia/reperfusion injury (IRI) are not fully defined. Here, we investigated the role of PTEN, a dual protein/lipid Phosphatase, in the development of ischemic AKI in mice. Pharmacological inhibition of PTEN with bpV(HOpic) exacerbated renal dysfunction and promoted tubular damage in mice with IRI compared with vehicle-treated mice with IRI. PTEN inhibition enhanced tubular cell Apoptosis in kidneys with IRI, which was associated with excessive Caspase-3 activation. Furthermore, PTEN inhibition expanded the infiltration of neutrophils and macrophages into kidneys with IRI, which was accompanied by increased expression of the proinflammatory molecules. These results have demonstrated that PTEN plays a crucial role in the pathogenesis of ischemic acute kidney injury through regulating tubular cell Apoptosis and inflammation suggesting PTEN could be a potential therapeutic target for acute kidney injury.

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