Related Experiment Video

Updated: May 2, 2026

Visualizing Angiogenesis by Multiphoton Microscopy In Vivo in Genetically Modified 3D-PLGA/nHAp Scaffold for Calvarial Critical Bone Defect Repair
09:34

Visualizing Angiogenesis by Multiphoton Microscopy In Vivo in Genetically Modified 3D-PLGA/nHAp Scaffold for Calvarial Critical Bone Defect Repair

Published on: September 7, 2017

8.6K

Mitogen-activated protein kinase phosphatase-1 promotes neovascularization and angiogenic gene expression

Joel D Boerckel1, Unnikrishnan M Chandrasekharan, Matthew S Waitkus

  • 1From the Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, OH (J.D.B., U.M.C., M.S.W., E.G.T., R.B., P.E.D.); and Department of Aerospace and Mechanical Engineering, University of Notre Dame, IN (J.D.B.).

Arteriosclerosis, Thrombosis, and Vascular Biology
|March 1, 2014
PubMed
Abstract

Insights

Mitogen-activated protein kinase phosphatase-1 (MKP-1) promotes new blood vessel formation (angiogenesis) by regulating gene transcription, not just by deactivating signaling molecules. This novel function highlights MKP-1 as a potential therapeutic target for neovascular diseases.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Vascular Biology

Background:

  • Angiogenesis, the formation of new blood vessels, is crucial for tissue repair and development.
  • Mitogen-activated protein kinases (MAPKs) are key regulators of angiogenesis.
  • Mitogen-activated protein kinase phosphatase-1 (MKP-1) typically inhibits MAPK signaling.

Purpose of the Study:

  • To investigate the role of MKP-1 in in vivo neovascularization.
  • To elucidate the underlying molecular mechanisms of MKP-1 in endothelial cells.

Main Methods:

  • Murine hindlimb ischemia model to study angiogenesis and arteriogenesis.
  • In vitro endothelial cell assays (migration, tube formation, proliferation) with MKP-1 depletion/deletion.
  • Chromatin immunoprecipitation sequencing to identify MKP-1 binding sites.
  • Analysis of histone modifications and gene expression (fractalkine).

Main Results:

  • MKP-1 deficiency impaired angiogenesis and arteriogenesis in vivo.
  • Endothelial MKP-1 is essential for vascular endothelial growth factor-induced cell migration, tube formation, and proliferation.
  • MKP-1 directly binds to the fractalkine gene locus, regulating histone H3 serine 10 dephosphorylation and fractalkine expression.
  • MKP-1 deletion reduced inflammatory cell infiltration, and fractalkine administration rescued neovascularization in MKP-1-deficient mice.

Conclusions:

  • MKP-1 acts as a positive regulator of angiogenic and arteriogenic neovascular growth.
  • A novel mechanism involves MKP-1 controlling gene transcription via histone modification.
  • MKP-1 represents a potential therapeutic target for promoting neovascularization.
Keywords:
MKP-1 phosphataseangiogenesis effect

More Related Videos

Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay09:03

Author Spotlight: Investigating Angiogenesis and Vessel Permeability Through a Modified Matrix Gel Plug Assay

Published on: June 30, 2023

1.7K
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

5.3K

Related Concept Videos

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...
2.9K
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...
5.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.3K
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...
4.7K
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...
3.6K