Loss of slit protein nephrin is associated with reduced antioxidant superoxide dismutase expression in podocytes shed from women with preeclampsia.

Yuping Wang, Shuang Zhao, Yang Gu, David F Lewis

Physiological reports 2018 Jul

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Recent findings of podocyte shedding/podocyturia highlight the central significance of podocyte injury in preeclampsia, a hypertensive disorder unique to human pregnancy. To test the hypothesis that oxidative stress contributes to kidney podocyte injury in preeclampsia, we specifically examined expression and distribution of antioxidant CuZn-SOD with nephrin and podoplanin in shed podocytes from women with preeclampsia. Human podocyte AB 8/13 cells served as control. We found that CuZn-SOD was localized at the front/outreach region of nephrin at the cell periphery (foot process areas) in control podocytes and expression of CuZn-SOD, nephrin, and podoplanin were all dislocated or lost in shed podocytes from preeclamptic patients. We further tested oxidative stress-induced nephrin shedding in podocytes, in which AB 8/13 podocytes were cultured under lowered oxygen condition (2%O2 ) or treated with hypoxic mimicking agent cobalt chloride. Our results showed that reduced nephrin and podoplanin expression were associated with downregulation of CuZn-SOD expression in podocytes when cells were cultured under lowered oxygen or hypoxic conditions. Nephrin shed in urinary specimen from preeclamptic women was also determined by immunoprecipitation/immunoblotting. The molecular sizes of nephrin that corresponded to that were lost when cells were cultured under hypoxic conditions. We concluded that increased oxidative stress plays a significant role in inducing podocyte protein shedding in preeclampsia. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Citation

Yuping Wang, Shuang Zhao, Yang Gu, David F Lewis. Loss of slit protein nephrin is associated with reduced antioxidant superoxide dismutase expression in podocytes shed from women with preeclampsia. Physiological reports. 2018 Jul;6(13):e13785