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Kidney Week

Abstract: PO0167

PTEN Protects Against Ischemia Reperfusion-Induced AKI via Regulating TNF-α Mediated Apoptosis

Session Information

  • AKI Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Wang, Huizhen, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
  • Li, Aiqing, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Background

Recently, PTEN, a vital tumor suppressor, has been raised its role in kidney homeostasis. We previous demonstrated that podocyte-specific knock-in of PTEN alleviated albuminuria and glomerulosclerosis in diabetic kidney disease. However, whether PTEN involves in acute kidney injury (AKI) remains unclear.

Methods

The levels of PTEN in renal tissue and serum were detected in ischemia-reperfusion (IR)-induced AKI mice with different ischemia time. Expression of PTEN was also detected in IR-induced cultured HK-2 injury with different ischemia and reperfusion time using ATP/glucose depletion that concentration of antimycin A mimicked the severity of ischemia. Immunoprecipitation and mass spectrometry were combined to analyze differential PTEN-interacting proteins among control, IRI+LV-NC and IRI+LV-PTEN groups. PTEN intervention including knock-down (si-PTEN) and knock-in (lentivirus-PTEN) was performed in HK-2 to reveal the role and mechanism of PTEN in IRI-AKI.

Results

PTEN was significantly reduced in renal tissue and serum in AKI mice at bilateral renal artery occlusion for 28 min and 35 min, and reperfusion for 1 day compared with sham group (P<0.05). Concentration of serum PTEN was negatively correlated with level of serum creatinine (r=-0.87, 95% CI: -0.94 to -0.71). PTEN was also downregulated in IR-induced HK-2 injury in an antimycin A concentration dependent manner (P<0.05). There were 23 upregulated (ACO2, BRCA1, USP30), and 20 downregulated (BIN1, pericentrin, SLC12A5) PTEN-interacting proteins in IRI+LV-PTEN group compared with IRI+LV-NC group. Gene Ontology enrichment analysis showed that overrepresentation of differential PTEN-interacting proteins functionally related to cytoskeleton, and ATPase activity. Pathway analysis showed a great role of differential PTEN-interacting proteins in apoptosis, and necroptosis. Knockdown of PTEN increased the expression of NGAL, CTGF and TNF-α in IR-induced HK-2 injury (P<0.05), while overexpression of PTEN alleviated IR-induced injury (P<0.05).

Conclusion

PTEN was decreased in renal tissue and serum associated with severity of renal injury in IRI-AKI mice, suggesting that PTEN is promising to be a serum biomarker for early prediction and evaluation of AKI. PTEN protected HK-2 from IR-induced injury possibly via regulating cytoskeleton and TNF-α mediated apoptosis signal.