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Updated: Jun 24, 2026

Generation of Patient-Derived Podocytes from Skin Biopsies
Published on: May 26, 2023
Downregulation of CD2-associated protein impaired the physiological functions of podocytes
Chun Zhang1, Hua-Jun Jiang, Ying Chang
1Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. drzhangchun@yahoo.com
Abstract:
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.
Insights
CD2-associated protein (CD2AP) is crucial for podocyte function. Reduced CD2AP levels impair cell adhesion, proliferation, and cytoskeleton integrity, leading to podocyte injury and potential proteinuria.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Medicine
Background:
- CD2-associated protein (CD2AP) is implicated in podocyte injury and proteinuria pathogenesis.
- The precise molecular mechanisms of CD2AP in podocyte function remain unclear.
Purpose of the Study:
- To investigate the role of CD2AP in maintaining podocyte integrity and function.
- To elucidate the molecular mechanisms underlying CD2AP's involvement in podocyte injury.
Main Methods:
- CD2AP gene knockdown using targeted siRNA in conditionally immortalized mouse podocytes.
- Assessment of cell adhesion, spreading, cell cycle progression, and proliferation.
- Analysis of F-actin distribution and nephrin expression/phosphorylation.
Main Results:
- CD2AP knockdown significantly reduced podocyte adhesion and spreading (P<0.05).
- Cell cycle arrest at G2/M phase and abnormal nuclear division were observed.
- Podocyte proliferation was significantly inhibited (P<0.05) with disordered F-actin and reduced nephrin expression/phosphorylation.
Conclusions:
- CD2AP plays a vital role in normal podocyte function.
- Reduced CD2AP levels induce podocyte injury by disrupting the cytoskeleton and the nephrin-CD2AP signaling pathway.
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