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Background <p>Septic acute kidney injury (AKI) is a common clinical complication associated with high mortality, and inflammation plays a central role in its pathophysiology. PARP7, a member of the poly ADP-ribose polymerase (PARP) family, functions as a negative feedback regulator of the IFN-I pathway by interacting with TBK1 in a mono-ADP-ribosylation-dependent manner.</p> Methods and results <p>In this study, we first confirmed upregulated PARP7 expression in septic AKI and found that increased PARP7 levels were predominantly localized in renal proximal tubular epithelial cells. We further demonstrated that global deletion of PARP7 exacerbated lipopolysaccharide (LPS)-induced renal inflammation and acute kidney injury, whereas specific overexpression of PARP7 in renal proximal tubular epithelial cells attenuated septic AKI in mice. Using single-cell RNA sequencing (scRNA-seq), we revealed that PARP7 suppresses the LPS-induced inflammatory response in renal tubular epithelial cells. Mechanistically, PARP7 interacts with TBK1 and mediates its ADP-ribosylation in LPS-stimulated renal tubular epithelial cells. The anti-inflammatory effects of PARP7 are primarily mediated through targeting TBK1 via its catalytic residue H532.</p> Conclusions <p>Collectively, our findings highlight the renoprotective role of PARP7 in AKI and provide a theoretical basis for developing therapies targeting the PARP7-TBK1 axis.</p> Graphical Abstract <p></p>

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PARP7 alleviates lipopolysaccharide-induced acute kidney injury by inhibiting TBK1-driven inflammation in renal tubular epithelial cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月9日

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  • Jiajun Xu,
  • Huihui Xie,
  • Zhouyang Zhu,
  • Yiting Lyu,
  • Xin Zhong,
  • Lintao Wang,
  • Jianing Zheng,
  • Ke Xu,
  • Jibo Han,
  • Lina Kang,
  • Xiaowen Shi

摘要

Background

Septic acute kidney injury (AKI) is a common clinical complication associated with high mortality, and inflammation plays a central role in its pathophysiology. PARP7, a member of the poly ADP-ribose polymerase (PARP) family, functions as a negative feedback regulator of the IFN-I pathway by interacting with TBK1 in a mono-ADP-ribosylation-dependent manner.

Methods and results

In this study, we first confirmed upregulated PARP7 expression in septic AKI and found that increased PARP7 levels were predominantly localized in renal proximal tubular epithelial cells. We further demonstrated that global deletion of PARP7 exacerbated lipopolysaccharide (LPS)-induced renal inflammation and acute kidney injury, whereas specific overexpression of PARP7 in renal proximal tubular epithelial cells attenuated septic AKI in mice. Using single-cell RNA sequencing (scRNA-seq), we revealed that PARP7 suppresses the LPS-induced inflammatory response in renal tubular epithelial cells. Mechanistically, PARP7 interacts with TBK1 and mediates its ADP-ribosylation in LPS-stimulated renal tubular epithelial cells. The anti-inflammatory effects of PARP7 are primarily mediated through targeting TBK1 via its catalytic residue H532.

Conclusions

Collectively, our findings highlight the renoprotective role of PARP7 in AKI and provide a theoretical basis for developing therapies targeting the PARP7-TBK1 axis.

Graphical Abstract