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Abstract: FR-PO711

Legumain Attenuates Podocyte Injury by Cleaving Transgelin and Stabilizing Cytoskeleton

Session Information

Category: Glomerular Diseases

  • 1304 Glomerular Diseases: Podocyte Biology

Authors

  • Qiu, Yang, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, China
  • Zhang, Chun, Huazhong University of Science and Technology Tongji Medical College, Wuhan, Hubei, China
Background

Legumain is a protease which functions diversely in various cell types. It plays significant role in renal tubular cells pathology. However, its participation in podocyte pathology has been rarely explored

Methods

We induced podocyte injury with adriamycin injection to mimic human FSGS in mice. In vivo, global legumain knockout mice, podocyte-specific legumain knockout mice and podocyte-specific legumain overexpression mice were applied. In vitro, lentivirus and adenovirus vectors were used to knockdown and overexpress legumain in podocytes. The substrate of legumain, transgelin, was exogenously expressed and then assayed for cleavage. Fragments effects were explored by importing plasmids expressing different transgelin protein domains into podocytes

Results

Firstly, legumain was upregulated in podocytes in FSGS model both in vivo and in vitro. Secondly, the knockout of legumain aggravated proteinuria, glomerular sclerosis and podocyte loss. The podocytes showed less nephrin, podocin and F-actin fibers, but higher desmin expression. The overexpression of legumain alleviated these pathologies. Furthermore, we found that transgelin, an actin binding protein, was negatively regulated by legumain. Its cleavage fragments showed less affinity to actin. Compared to full length transgelin,the fragments inactived RhoA/Rock pathway and upregulated F-actin and paxillin in podocytes

Conclusion

Legumain protects podocytes by cleaving transgelin and stabilizing cytoskeleton. This strongly suggests a therapeutic role of legumain in FSGS