Molecular Mechanism of the YAP1/ANXA2 Signaling Axis in Regulating Apoptosis and Migration of Renal Tubular Epithelial Cells

Shaoting SUN; Lanmei LI; Weiwei BAI; Na CHEN; Meng WANG; Ming ZHANG; Yafen LI

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Shaoting SUN, Lanmei LI, Weiwei BAI, Na CHEN, Meng WANG, Ming ZHANG, Yafen LI. Molecular Mechanism of the YAP1/ANXA2 Signaling Axis in Regulating Apoptosis and Migration of Renal Tubular Epithelial Cells[J]. Journal of Kunming Medical University.

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Molecular Mechanism of the YAP1/ANXA2 Signaling Axis in Regulating Apoptosis and Migration of Renal Tubular Epithelial Cells

1.
Department of Nephrology
2.
Department of Medical Affairs，Cangzhou People’s Hospital ，Cangzhou Hebei 061000，China

Received Date: 2025-08-18
Available Online: 2025-11-01

Abstract

Abstract

Objective To investigate the molecular mechanism by which YAP1, the core effector of the Hippo pathway, regulates its downstream effector ANXA2 in renal injury, and to elucidate the role of the YAP1/ANXA2 axis in renal tubular epithelial cell repair. Methods A YAP1-overexpressing HK-2 cell model was established. Co-immunoprecipitation （Co-IP） combined with mass spectrometry was used to screen for YAP1-interacting proteins. ANXA2 expression was knocked down using siRNA interference. Cell migration ability was assessed via Transwell migration assays, and apoptosis levels were detected by flow cytometry （Annexin V-FITC/PI staining）. The regulatory effect of YAP1 on ANXA2 promoter transcriptional activity was verified using a dual-luciferase reporter gene assay. Results YAP1 overexpression significantly enriched ANXA2 and formed a stable complex （P < 0.01）. Silencing of ANXA2 significantly increased the rates of early and late apoptosis （P < 0.001） and markedly reduced the number of migrating cells （P < 0.01）. The dual-luciferase reporter assay confirmed that YAP1 directly activates ANXA2 promoter and enhances its transcriptional activity （P < 0.001）. Conclusion YAP1 directly binds to the ANXA2 promoter and enhances its transcription, thereby inhibiting apoptosis and promoting migration of renal tubular epithelial cells, highlighting the YAP1/ANXA2 axis as a critical regulator of renal injury repair. This study provides a novel potential target for mitigating renal fibrosis.
- YAP1,
- ANXA2,
- Renal injury,
- Apoptosis,
- Epithelial-mesenchymal transition,
- Transcriptional regulation

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References(25)

References

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