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Abstract: SA-PO574

Fibroblast mTORC2/PPARγ-Dependent HGF Production Protects Against Tubular Cell Death and AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Yuan, Gui, Nanjing medical university, Nanjing, China
  • Dai, Chunsun, Nanjing medical university, Nanjing, China

Kidney interstitial fibroblasts play a crucial role in dictating tubular cell fate and the outcome of acute kidney injury (AKI). However, the underlying mechanisms remain to be further determined.


Mouse model with inducible Rictor gene deletion in fibroblast was generated. Kidney ischemia/reperfusion injury was employed to induce acute kidney injury in mice.


Here, we found that Rictor/mTORC2 signaling was activated in mouse kidney interstitial fibroblasts after ischemia/reperfusion injury (IRI). Ablation of Rictor in fibroblasts led to more severe kidney dysfunction and morphological damage in mice after IRI compared to their littermate controls. More tubular cell apoptosis and inflammatory cell accumulation were detected in the knockout kidneys after IRI. In in vitro, a co-culture system between fibroblasts and tubular cells was generated. Blockade of Rictor/mTORC2 signaling in fibroblasts with Rictor gene ablation or pharmacological inhibition facilitated staurosporine-induced tubular cell death. In addition, blocking fibroblast mTORC2 signaling could downregulate its peroxisome proliferator-activated receptor gamma (PPARγ) and hepatocyte growth factor (HGF) expression, as well as attenuate c-met signaling activation in tubular cells. Moreover, activation of fibroblast PPARγ could augment HGF expression and attenuate tubular cell death. Notably, in mouse kidneys, ablation of fibroblast Rictor reduced the PPARg and HGF expression. The tyrosine phosphorylation of HGF receptor c-met was also diminished in the knockout kidneys after IRI.


Together, these data suggests that Rictor/mTORC2 signaling activation in kidney interstitial fibroblasts may protect against tubular cell death and dictate the outcome of acute kidney injury through PPARγ-stimulated HGF production.


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