Downregulation of CD2-associated protein impaired the physiological functions of podocytes.
Emerging evidences show that CD2-associated protein (CD2AP) is involved in podocyte injury and the pathogenesis of proteinuria. However, the exact molecular mechanism by which CD2AP exerts its biological function is elusive. We knocked down CD2AP gene by target siRNA in conditionally immortalized mouse podocytes, which showed lowered cell adhesion and spreading ability (P<0.05). At the same time, cell cycle was arrested in G2/M phase (P<0.05), and pathologic nuclear division could easily be seen in CD2AP siRNA-transfected podocytes. The proliferation of podocytes were also inhibited significantly by CD2AP siRNA transfection (P<0.05). Further study revealed disordered distributions of F-actin, as well as lowered nephrin expression and phosphorylation in podocytes. These data suggest that CD2AP may play a crucial role in maintaining the normal function of podocytes and lowered CD2AP causes podocyte injury by disrupting the cytoskeleton and disturbing the nephrin-CD2AP signaling pathway.
Zhang
Chun
C
Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. drzhangchun@yahoo.com
Jiang
Hua-Jun
HJ
Chang
Ying
Y
Fang
Zhan
Z
Sun
Xi-Feng
XF
Liu
Jian-She
JS
Deng
An-Guo
AG
Zhu
Zhong-Hua
ZH
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton; D015536:Down-Regulation; D016195:G2 Phase; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C113267:nephrin