Related Experiment Video

Updated: Jun 6, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

346

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

Jian Jiao1, Deng Zhang1, Jianbo Peng1

  • 1Department of Vascular Surgery, Fengyang County People's Hospital, Chuzhou, Anhui 233100, P.R. China.

Molecular Medicine Reports
|November 22, 2024
PubMed

Insights

Murine double minute-2 (MDM2) and phosphatase and tensin homolog (PTEN) are upregulated in deep vein thrombosis (DVT). Their interaction inhibits endothelial cell development, promoting DVT via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway.

Area of Science:

  • Vascular Biology
  • Molecular Medicine
  • Thrombosis Research

Background:

  • Deep vein thrombosis (DVT) significantly impacts patient quality of life and can lead to post-thrombotic syndrome.
  • Understanding the molecular mechanisms underlying DVT pathogenesis is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the interplay between murine double minute-2 (MDM2) and phosphatase and tensin homolog (PTEN) in the context of DVT.
  • To elucidate the role of MDM2 and PTEN in endothelial cell function and DVT development.

Main Methods:

  • Analysis of MDM2 and PTEN expression in venous blood from DVT patients.
  • In vitro studies using oxidized low-density lipoprotein-treated human umbilical vein endothelial cells (HUVECs) with MDM2 or PTEN knockdown.
  • Verification of MDM2-PTEN interaction using STRING analysis and co-immunoprecipitation assays.
  • Evaluation of PTEN's role in the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway using KEGG and STRING analysis.
  • Assessment of the effect of JAK/STAT signaling inhibition (AG-490) on HUVEC behavior.

Main Results:

  • Both MDM2 and PTEN were found to be upregulated in DVT patients.
  • Knockdown of MDM2 or PTEN enhanced HUVEC proliferation, migration, invasion, apoptosis, and angiogenesis.
  • MDM2 silencing led to a decrease in PTEN levels, suggesting a regulatory relationship.
  • PTEN was confirmed to inhibit the JAK/STAT signaling pathway.
  • Inhibition of JAK/STAT signaling reversed the protective effects of PTEN knockdown on HUVECs.

Conclusions:

  • MDM2 and PTEN are upregulated in DVT and interact to promote the condition.
  • The MDM2-PTEN interaction appears to inhibit endothelial cell development by suppressing the JAK/STAT signaling pathway.
  • These findings offer novel insights into the collaborative role of MDM2 and PTEN in DVT pathogenesis.
Keywords:
Janus kinase/signal transducer and activator of transcription pathwaydeep vein thrombosismurine double minute‑2phosphatase and tensin homolog

More Related Videos

A Patient-Derived Xenograft Model for Venous Malformation06:51

A Patient-Derived Xenograft Model for Venous Malformation

Published on: June 15, 2020

5.3K
Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay11:38

Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay

Published on: September 14, 2021

3.3K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.4K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K