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Abstract: FR-PO946

Upregulated LRRC55 Aggravates Podocyte Injury Through Activating the BK Channel

Session Information

Category: Glomerular Diseases

  • 1204 Podocyte Biology

Authors

  • Hu, Shuai, Nanjing University School of Medicine, Nanjing, China
  • Han, Runhong, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • Chen, Long, National Standard Laboratory of Pharmacology for Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
  • Bao, Hao, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
  • Liu, Zhihong, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
Background

Focal segmental glomerulosclerosis (FSGS) is a common podocytopathy, accounting for 40% of cases of nephrotic syndrome in adults, andits pathogenesis has not been fully elucidated. LRRC55 is a γ subunit of the BK channel, and the role of LRRC55 in podocyte injury has not been studied.

Methods

Glomerular tissues of FSGS patients and controls were isolated and subjected to transcriptome analysis. Cell biology techniques were used to analyze LRRC55 expression, BK channel current, intracellular potassium level, caspase-3 activation, DNA fragmentation and podocyte apoptosis in human podocytes and Ang II-treated mice.

Results

Based on transcriptome analysis and confirmation study, the level of LRRC55 was significantly increased in glomerular podocytes in FSGS patients. In vitro, treatment with Ang II induced NFATc nuclear translocation and promoted LRRC55 upregulation in podocytes. The upregulated LRRC55 and increased intracellular calcium led to BK channel activation and the loss of intracellular potassium, which caused caspase-3 activation and DNA fragmentation in Ang II-treated podocytes.In contrast, silencing of LRRC55 reversed the intracellular potassium loss, caspase-3 activation and DNA fragmentation in the Ang II-treated podocytes. In vivo, Ang II-infusion caused an obvious increase in LRRC55 expression, BK channel activation, intracellular potassium decrease, podocyte apoptosis and focal segmental sclerosisin mice. Knockout of BK channel or silencing of LRRC55 prevented intracellular potassium decrease and ameliorated podocyte injury and focal segmental sclerosis in Ang II-treated mice.

Conclusion

The results suggest that the upregulated LRRC55 aggravates podocyte injury through activating BK channel. Inhibition of LRRC55 attenuates podocyte injury, may representing a new therapeutic approach for FSGS patients.