Cdk1/p53/p21 feedback loop mechanisms in the pathogenesis of interstitial cystitis/bladder pain syndrome.
Biochim Biophys Acta Mol Basis Dis
; 1870(7): 167305, 2024 10.
Article
in En
| MEDLINE
| ID: mdl-38880159
ABSTRACT
PURPOSE:
This study aimed to elucidate the role of the Cdk1/p53/p21 feedback loop in the pathogenesis of interstitial cystitis (IC)/bladder pain syndrome (BPS). MATERIALS ANDMETHODS:
An IC/BPS cell model was established. Cell viability was determined using the CCK-8 assay. Flow cytometry was adopted to assess cell apoptosis rates. ELISA was employed to measure secretion levels of inflammatory factors (IL-6, IL-8, and TNF-α). Gene expressions were assessed using PCR, while protein expressions were analyzed through Western blotting analysis. Epithelial permeability was demonstrated using the phenol red leakage experiment and FITC-dextran permeability assay. The interaction between proteins was determined using co-immunoprecipitation, and protein localization was investigated using immunofluorescence.RESULTS:
The CCK-8 assay revealed a significantly reduced viability of IC/BPS cells compared to normal epithelial cells (p < 0.05). Elevated levels of IL-6, IL-8, and TNF-α were detected in IC/BPS cells. Changes in the expressions of E-cadherin and ZO-1 were evident, leading to increased epithelial permeability in IC/BPS cells. Furthermore, within IC/BPS cells, Cdk1 phosphorylated p53 in the nucleus. The Cdk1/p53/p21 feedback loop was established to influence urothelial permeability. Both p21 and Cdk1 inhibitors notably reduced the epithelial permeability in IC/BPS cells.CONCLUSION:
The Cdk1/p53/p21 feedback loop was instrumental in IC/BPS, acting as a regulator of urothelial permeability. This discovery offered a novel therapeutic approach for IC/BPS management.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CDC2 Protein Kinase
/
Tumor Suppressor Protein p53
/
Cystitis, Interstitial
Limits:
Humans
Language:
En
Journal:
Biochim Biophys Acta Mol Basis Dis
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: