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Abstract: FR-PO1193

Lp-PLA2 Promotes Tubulointerstitial Inflammation and Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Zhou, Jie, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • Yuan, Ren, Huashan Hospital Fudan University, Shanghai, China
  • Huang, Haowen, Huashan Hospital Fudan University, Shanghai, China
  • Xue, Jun, Huashan Hospital Fudan University, Shanghai, China
Background

Inflammation and fibrosis are critical in kidney injury, often causing irreversible damage. Macrophage infiltration is central to this process. Lp-PLA2, encoded by PLA2G7 in macrophages, produces pro-inflammatory lipids that promote oxidative stress and inflammation. While Lp-PLA2 is a known risk factor for atherosclerosis and other inflammatory conditions, its role in tubulointerstitial injury remains unclear.

Methods

WT mice received the Lp-PLA2 inhibitor SR1376 post-UIR, and PLA2G7-/- mice underwent UIR. All were analyzed at 21d for Lp-PLA2’s pro-inflammatory and pro-fibrotic effects.
Bumpt cells were exposed to hypoxia for 24 h and co-cultured with PLA2G7-overexpressing or knockout macrophage cell(Raw264.7-OE and Raw264.7-KO) to evaluate Lp-PLA2–mediated tubulointerstitial inflammation and fibrosis.

Results

Inflammation and fibrosis were markedly reduced in SR1376-treated and PLA2G7-/- mice. Co-culture with Raw264.7-OE cells leading to higher ROS levels and upregulated expression of inflammatory and fibrotic markers in Bumpt cells.

Conclusion

This study employed multiple experimental approaches to elucidate the critical role of Lp-PLA2 in renal tubulointerstitial inflammation and fibrosis.

Evaluation of renal inflammation and fibrosis levels

Assessment of renal tubular epithelial cell injury

Digital Object Identifier (DOI)