Abstract: FR-PO589

Triptolide Alleviates Podocyte Injury in Hyperglycemia via Abrogating Activation of NALP3 Inflammasome and PI3K/Akt/mTOR Signaling

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Han, Wenbei, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
  • Wan, Yigang, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
Background

Triptolide (TP), an extracted phytomedicine is frequently used for protecting against podocyte injury in early diabetic kidney disease (DKD) in China. However, the therapeutic mechanism remains unclear. In the process of DKD, the activation of NALP3 inflammasome and PI3K/Akt/mTOR signaling in kidneys is the important mechanisms by which renal inflammation contributes to podocyte damage. This study thereby aimed to examine the ameliorative effects of TP on podocyte lesion in hyperglycemia (HG), then to clarify its anti-inflammatory mechanisms in vitro by inhibiting the activation of NALP3 inflammasome and PI3K/Akt/mTOR signaling.

Methods

HG was used to induce murine podocyte to be in the state of damage. After the intervention of HG for 0, 3, 6, 12, 24 and 48 hours, firstly, the protein expressions of NALP3, active caspase-1 and active IL-1β were detected. Secondly, the protein expressions of desmin and synaptopodin were examined. Thirdly, the protein expressions of p-PI3K, p-Akt and p-mTOR were observed. And then, after the co-treatment of TP and HG without or with mTOR inhibitor (rapamycin), the protein expressions of the key factors in NALP3 inflammasome activation, podocyte lesion and PI3K/Akt/mTOR signaling pathway were tested, respectively.

Results

The result showed that HG induced up-regulation of NALP3, active caspase-1, active IL-1β, p-PI3K, p-Akt and p-mTOR, and down-regulation of desmin and synaptopodin at protein expression level in podocyte. The co-treatment of TP and HG reversely regulated the protein expressions of NALP3, active IL-1β, desmin, synaptopodin, p-Akt and p-mTOR in HG-intervened podocyte significantly. The co-treatment of rapamycin, TP and HG recovered the level of NALP3 and p-mTOR protein expressions in HG-intervened podocyte obviously.

Conclusion

In conclusion, TP, as a natural regulator, attenuates podocyte injury in HG by abrogating the activation of NALP3 inflammasome and PI3K/Akt/mTOR signaling. This study may provide the first evidence that TP directly protects podocyte in HG via anti-inflammation.

Funding

  • Government Support - Non-U.S.