TP53 Promotes Pyroptosis and Inhibits Cell Invasion and Migration through the MMP1 Signaling Pathway in NIH-3T3 Cells

Ming YANG; Xiaoxing LYU; Shunli XU

doi:10.12259/j.issn.2095-610X.S20250607

Volume 46 Issue 6

Jun. 2025

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Ming YANG, Xiaoxing LYU, Shunli XU. TP53 Promotes Pyroptosis and Inhibits Cell Invasion and Migration through the MMP1 Signaling Pathway in NIH-3T3 Cells[J]. Journal of Kunming Medical University, 2025, 46(6): 54-63. doi: 10.12259/j.issn.2095-610X.S20250607

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Ming YANG, Xiaoxing LYU, Shunli XU. TP53 Promotes Pyroptosis and Inhibits Cell Invasion and Migration through the MMP1 Signaling Pathway in NIH-3T3 Cells[J]. Journal of Kunming Medical University, 2025, 46(6): 54-63. doi: 10.12259/j.issn.2095-610X.S20250607

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TP53 Promotes Pyroptosis and Inhibits Cell Invasion and Migration through the MMP1 Signaling Pathway in NIH-3T3 Cells

doi: 10.12259/j.issn.2095-610X.S20250607

1.
Department of Burn and Plastic Surgery，The Second Affiliated Hospital，Air Force Military Medical University，Xi’an Shaanxi 710000
2.
Department of Orthopaedics，The First People’s Hospital of Xinxiang City/The Fifth Clinical College of Xinxiang Medical College，Xinxiang Henan 453000，China

Received Date: 2025-03-11
Publish Date: 2025-06-25

Abstract

Abstract

Objective To explore the molecular mechanism by which TP53 regulating pyroptosis, invasion and migration of embryonic fibroblasts through MMP1/NLRP3 signaling pathway. Methods NIH-3T3 murine embryonic fibroblasts were transfected with lentivirus and grouped as Control, Vector, oeTP53, oeTP53+shNC, and oeTP53+shMMP1. Cell proliferation and viability were assessed via CCK-8 assay, apoptosis by flow cytometry, and migration/invasion through scratch and invasion experiments. Protein interaction between P53 and MMP1 was confirmed by Co-immunoprecipitation. RT-qPCR evaluated mRNA expression of TP53, Collagen I, Collagen III, and α-SMA, while Western blot analyzed protein levels of these markers and pyroptosis-related proteins. Transmission electron microscopy was employed to examine cellular pyroptotic body modifications. Results Compared with Control and Vector groups, the oeTP53 group showed reduced cell proliferation activity （P < 0.01）, increased cell apoptosis rate （P < 0.0001）, decreased invasion （P < 0.0001） and migration capabilities （P < 0.0001）; reduced Collagen I （P < 0.001）, Collagen III （P < 0.01）, and α-SMA （P < 0.01） protein expressions; increased NLRP3 （P < 0.05） and cleaved-caspase-1 expressions （P < 0.01）; and numerous pyroptotic bodies. MMP1 protein levels were found to be elevated in the oeTP53 group （P < 0.05）, and Co-IP demonstrated an interaction between p53 and MMP1 proteins. Compared with oeTP53 group, the oeTP53+shMMP1 group showed increased cell viability （P < 0.001）, decreased cell apoptosis rate （P < 0.01）, and increased cell migration （P < 0.01） and invasion capabilities （P < 0.01）, increased scar formation-related protein expressions of Collagen I （P < 0.01）, Collagen III （P < 0.001）, and α-SMA （P < 0.05）; decreased pyroptosis-related protein expressions of NLRP3 （P < 0.01） and cleaved-caspase-1 （P < 0.001）; and reduced pyroptotic bodies. Conclusion Overexpression of TP53 can inhibit mouse embryonic fibroblast proliferation, migration, and invasion, reduce scar formation-related protein expressions, and promote cell pyroptosis, with its mechanism potentially related to the MMP1/NLRP3 pathway.
- TP53,
- MMP1,
- Post-burn scar formation,
- Scar formation,
- Pyroptosis

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References(21)

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