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Effect of the knockdown of Cabin1 on p53 in glomerular podocyte
Yueqiang Wen1, Peilan Zhou1, Lingling Liu2
1a Department of Nephrology , The Second Affiliated Hospital, Guangzhou Medical University , Guangzhou , P.R. China and.
Abstract:
Calcineurin binding protein 1 (Cabin1) is a natural inhibitor of calcineurin (CN). Moreover, Cabin1 retards tumor cell apoptosis by regulating p53. This study was designed to observe the expression of Cabin1 during podocyte injury, as well as its relationship with p53. Sprague-Dawley rats were used for the establishment of 5/6 nephrectomized rat model. Sham-operated rats underwent ventral laparotomy without nephrectomy. Then, rats were sacrificed at 8 and 12 weeks after nephrectomy. WT-1, a podocyte nuclear protein, was used for indicating the localization of Cabin1 in glomeruli. As tacrolimus protects podocyte via inhibiting AngiotensinII (AngII) induced CN activation. Cultured podocytes were injured by AngII or restored by tacrolimus. The protein expression and localization was detected by western blot or immunofluorescence staining. Cabin1 was knocked down by siRNA in cultured podocytes. In 5/6 nephrectomized rats, the colocalization of Cabin1 and WT-1 became more obviously in podocyte nuclei. Cabin1 protein was markedly increased in rats at 8 and 12 weeks after nephrectomy, as well as in AngII injured podocytes at 48 h (0.99 ± 0.12 in AngII group versus 0.80 ± 0.16 in control group). Cabin1 and p53 colocalized in cultured podocyte nuclei, p53 expression was significantly decreased (0.21 ± 0.05 in siRNA group versus 0.31 ± 0.05 in negative control group) after Cabin1 was being knocked down. In conclusion, Cabin1 expression significantly increases during podocyte injury. Knockdown of Cabin1 induces p53 expression decrease in cultured podocyte. Cabin1 may provide a new target to investigate podocyte injury.
Insights
Calcineurin binding protein 1 (Cabin1) increases during podocyte injury and may be a new target for treatment. Cabin1 knockdown reduces p53 expression in podocytes, suggesting a role in kidney disease progression.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Calcineurin binding protein 1 (Cabin1) inhibits calcineurin (CN) and regulates p53, affecting tumor cell apoptosis.
- Podocyte injury is a key factor in kidney disease progression.
- Understanding Cabin1's role in podocyte injury is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the expression of Cabin1 during podocyte injury.
- To determine the relationship between Cabin1 and p53 in podocytes.
- To explore Cabin1 as a potential therapeutic target for podocyte injury.
Main Methods:
- Established a 5/6 nephrectomized rat model and used sham-operated rats as controls.
- Utilized WT-1 to indicate Cabin1 localization in glomeruli.
- Injured cultured podocytes with Angiotensin II (AngII) and treated with tacrolimus.
- Detected protein expression and localization via western blot and immunofluorescence staining.
- Knocked down Cabin1 using siRNA in cultured podocytes.
Main Results:
- Cabin1 colocalized with WT-1 in podocyte nuclei in nephrectomized rats.
- Cabin1 protein levels were significantly increased in nephrectomized rats and AngII-injured podocytes.
- Cabin1 and p53 colocalized in podocyte nuclei, and Cabin1 knockdown decreased p53 expression.
Conclusions:
- Cabin1 expression is significantly upregulated during podocyte injury.
- Cabin1 knockdown leads to decreased p53 expression in cultured podocytes.
- Cabin1 represents a potential novel target for investigating and treating podocyte injury.
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