ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: TH-PO691

MAD2B-Numb Interaction Is Involved in High Glucose Induced Podocyte Injury by Regulating Cell Polarity

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental


  • Su, Hua, Huazhong Science and Technology University, Wuhan, China
  • Tang, Hui, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • Zhang, Chun, Union Hospital, Huazhong University of Science and Technology, Wuhan Hubei Provicne, China

The loss of podocyte is a critical event in the pathogenesis of diabetic nephropathy (DN). Recent studies have demonstrated the importance of cell polarity in the maintenance of podocyte architecture. Previously, our group found the mitotic arrest deficient protein MAD2B is implicated in high glucose (HG) induced podocyte injury. However, the exact mechanism of MAD2B in podocyte injury still remains to be established.


Patients diagnosed with DN were enrolled in this study, and DN model was constructed on C57BL/6 mice by a single intra-peritoneal injection of STZ. In vitro study, immortalized human podocyte cell line was employed, and exposed to different treatments after differentiation. The expression of MAD2B and Numb was suppressed by recombinant lentivirus infection.


Previously we have demonstrated the enhancement of MAD2B in DN mice and HG treated podocytes. Using a yeast two-hybrid interaction trap we identified Numb as a novel MAD2B binding protein in human kidney. Through confocal laser scanning microscopy we confirmed the co-localization of MAD2B and Numb in podocyte in vivo and in vitro. Subsequent endogenous co-immunoprecipitation established the direct interaction between MAD2B and Numb. HG exposure upregulated MAD2B expression and Numb phosphorylation in podocyte. Interestingly, HG also induced Numb translocation from podocyte basolateral membrane to cytoplasm, which accompanied by podocyte cytoskeleton re-organization. MAD2B genetic deletion partly reversed Numb phosphorylation and cytoplasm translocation as well as cytoskeleton re-organization in podocyte. In addition, Numb bound to integrin-β1 and correlated with its basolateral membrane distribution. But this binding was greatly disrupted by HG or phosphatase inhibitor calyculin-A or Numb depletion.


Upregulated MAD2B expression accelerates Numb phosphorylation and its translocation from podocyte basolateral membrane to cytoplasm in HG condition. Phosphorylated Numb has a reduced binding affinity to integrin-β1 which diminishes integrin-β1 distribution on podocyte basolateral membrane and ultimately leads to the loss of cell polarity and podocyte injury.


  • Government Support - Non-U.S.