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α-Actinin-4 is involved in the process by which dexamethasone protects actin cytoskeleton stabilization from adriamycin-induced podocyte injury

Authors

  • HAIMEI LIU,

    1. Department of Nephrology and Rheumatology, Children's Hospital of Fudan University
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    • These authors contributed equally to this work and should be considered co-first authors.

  • XIA GAO,

    1. Department of Nephrology and Rheumatology, Children's Hospital of Fudan University
    2. Department of Pediatrics, People's Hospital of Gansu Province, Lanzhou, China
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    • These authors contributed equally to this work and should be considered co-first authors.

  • HONG XU,

    Corresponding author
    1. Department of Nephrology and Rheumatology, Children's Hospital of Fudan University
      Professor Hong Xu, Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, 399 WanYuan Road, Shanghai, 201102, China. Email: hxu@shmu.edu.cn
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  • CHUN FENG,

    1. Institutes of Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
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  • XINYU KUANG,

    1. Department of Nephrology and Rheumatology, Children's Hospital of Fudan University
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  • ZENGXIA LI,

    1. Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai
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  • XILIANG ZHA

    1. Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai
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Professor Hong Xu, Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, 399 WanYuan Road, Shanghai, 201102, China. Email: hxu@shmu.edu.cn

ABSTRACT:

Aim:  Glucocorticoid therapy has been used in childhood nephrotic syndrome since the 1950s, where the characteristic change is effacement of the actin-rich foot process of glomerular podocytes. Recent studies have shown that glucocorticoids, in addition to their general immunosuppressive and anti-inflammatory effects, have a direct effect on podocytes, regulate some apoptotic factors, and increase the stability of actin filaments. However, the precise mechanism(s) underlying the protective effects of glucocorticoids on podocytes remain unclear. It is known that adriamycin (ADR) can induce podocyte foot process effacement and trigger massive proteinuria in rodent models. However, few reports have examined the direct role of ADR in podocyte actin rearrangement in vitro. In this study, we investigated how ADR directly induced podocyte actin cytoskeleton rearrangement and further analyzed how dexamethasone prevented such injury.

Methods:  We used confocal microscopy to assess podocyte actin rearrangement. Western blot analysis and real-time polymerase chain reaction were performed to measure the protein and mRNA levels of α-actinin-4.

Results:  We demonstrated that there was a time-dependent ADR-induced podocyte actin rearrangement with less than 12 h of ADR treatment in cultured podocytes. Dexamethasone could protect podocytes from ADR-induced injury and also stabilize the expression of α-actinin-4.

Conclusion:  This study showed that dexamethasone had direct effects on podocytes: α-actinin-4 may be one of the potential target molecules.

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