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Kidney Week

Abstract: PO0155

Six1 Activation Is Involved in Cell Proliferation and Migration and Anti-Inflammation of Acute Ischemia-Reperfusion Injury in Mice

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


  • Jin, Yong, Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
  • Wan, Xin, Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
  • Cao, Changchun, Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

Nephrogenic proteins are re-expressed during the regeneration process after ischemia reperfusion (IR) injury, while the role of these proteins in the repair of kidney injury is still unknown. We found that Six1, a developmentally regulated homeoprotein is reactivated in tubular epithelial cells (TECs) after IR injury.


We established Six1 overexpresstion cell lines to confirm its effect on kidney repair in vitro. Cell proliferation and cell migration was detected by flow cytometry and cell migration assays respectively. Luciferase reporter assay was used to measure the anti-inflammation capacity of Six1 overexpressing cells, and chromatin immunoprecipitation (ChIP)-qPCR was used to analyze Six1 protein occupancy of the indicated genes. In vivo, we injected adeno-associated viral vector serotype 9 (AAV9)-Six1 into uninjured renal pelvis before IR injury, then assessed morphologic and functional parameters and gene expression in IR injury kidney.


We demonstrated that Six1 promoted cell proliferation by upregulating cyclin and glycolytic genes, and that cell migration through increasing the expression of matrix metalloproteinases (MMPs) in the cell model. Notably, the overexpression of Six1 could suppress inflammation through NF-κB-mediated pathway. Six1 target the promoters of amino-terminal enhancer of split (AES) and translocated in liposarcoma (TLS), which are cofactors of NF-κB subunit RelA, and then inhibit the transactivation function of RelA in a negative feedback circuit. Six1 overexpression resulted in inhibiting inflammation and promoting cell proliferation to reduce kidney damage of mice from IR injury in vivo.


Our studies suggested that Six1 promoted kidney recovery and regeneration through cell proliferation/migration and anti-inflammation which might be a potential therapeutic target that can be used to improve kidney repair after IR injury.


  • Government Support - Non-U.S.