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Abstract: FR-PO411

The Effects of Modulating Autophagy on Macrophages Adhesion and Migration in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Jiang, Yuteng, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Zhu, Xiaodong, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Zhao, Yu, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Liu, Yuqiu, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Wu, Beibei, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
  • Zhang, Xiaoliang, Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, China
Background

Macrophage infiltration is an important histopathological feature of various chronic renal diseases including diabetic nephropathy. This study aims to investigate the impact of macrophages adhesion and migration by modulating autophagy.

Methods

In vivo, rats were randomly distributed into control (NC) and diabetic nephropathy (DN) groups. The pathological changes in renal tissue were assessed, and expression of CD68, LC3, P62 were analysed. In vitro, RAW264.7 cells were divided into normal and high glucose (HG, 30mM) groups. The capacity for macrophage adhesion and migration and the expression of autophagy markers were observed with and without autophagy modulators (rapamycin, 3-methyladenine, chloroquine, and bafilomycin A1 for RAPA, 3-MA, CQ, BAFA). The numbers of autophagosomes and the process of degradation and fusion of autophagosome-lysosome were observed by electron microscopy.

Results

In vivo, renal injury is aggravated in diabetic rat compared with NC group. The expression levels of CD68 and P62 of renal tissues increased in DN group, while expression level of LC3 decreased. In vitro, HG or 3-MA reduce the numbers of autophagosomes with less expression of LC3 and Beclin-1, but increase expression of P62. HG or 3-MA promote the adhesion and migration capacity of macrophages. Moreover, CQ and BAFA inhibit the process of degradation and fusion of the autophagosome-lysosome as well as the expression of LC3 and Beclin-1. We notice an increase expression of P62 by CQ and BAFA stimulaion. These effects further facilitate the adhesion and migration capacity of macrophages. However, RAPA increases the numbers of macrophage autophagosomes, resulting in an increase expression of LC3 and Beclin-1, whereas a reduction expression of P62, which lead to inhibition of adhesion and migration of macrophages induced by HG (P<0.05).

Conclusion

Modulating the function of autophagy can affect the adhesion and migration capacity of macrophages in diabetic nephropathy.

Funding

  • Government Support - Non-U.S.