MDM2 interacts with PTEN to inhibit endothelial cell development and promote deep vein thrombosis via the JAK/STAT signaling pathway

Jiao,Jian; Zhang,Deng; Peng,Jianbo; Li,Yunsai

doi:10.3892/mmr.2024.13397

MDM2 interacts with PTEN to inhibit endothelial cell development and promote deep vein thrombosis via the JAK/STAT signaling pathway

Authors:
- Jian Jiao
- Deng Zhang
- Jianbo Peng
- Yunsai Li
View Affiliations

Affiliations: Department of Vascular Surgery, Fengyang County People's Hospital, Chuzhou, Anhui 233100, P.R. China
Published online on: November 18, 2024 https://doi.org/10.3892/mmr.2024.13397
Article Number: 31
Copyright: © Jiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Deep vein thrombosis (DVT) is a prevalent clinical condition, which markedly affects patients' quality of life, commonly leading to post‑thrombotic syndrome. The present study aimed to elucidate the intricate interplay between murine double minute‑2 (MDM2) and phosphatase and tensin homolog (PTEN), thus shedding new light on their role in the pathogenesis of DVT. The results showed that both MDM2 and PTEN were upregulated in venous blood samples obtained from patients with DVT. However, MDM2 or PTEN knockdown markedly increased the proliferation, migration, invasion, apoptosis and angiogenesis of oxidized low‑density lipoprotein‑treated human umbilical vein endothelial cells (HUVECs). Furthermore, MDM2 silencing downregulated PTEN. The association between MDM2 and PTEN was verified through comprehensive analyses, including Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis and co‑immunoprecipitation assays. The effect of PTEN on DVT was evaluated by Kyoto Encyclopedia of Genes and Genomes and STRING analysis, which demonstrated that PTEN displayed an inhibitory role in the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. Notably, treatment with AG‑490, an inhibitor of JAK/STAT signaling, reversed the protective effect of PTEN knockdown on the behavior of HUVECs. In summary, the results of the current study indicated that both MDM2 and PTEN were upregulated in patients with DVT. The interaction between MDM2 and PTEN was also verified, thus providing novel insights into their potential collaborative role in the development of DVT. Overall, MDM2 and PTEN may interact to inhibit endothelial cell development and promote the occurrence of DVT via inhibiting the JAK/STAT signaling pathway.

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