Related Experiment Video

Updated: Jun 25, 2025

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

7.9K

Jagged1-Notch1 Signaling Pathway Induces M1 Microglia to Disrupt the Barrier Function of Retinal Microvascular

Xiyu Wu1,2, Haoxian Zhu1,2, Junbin Liu2

  • 1School of Medicine, South China University of Technology, Guangzhou, China.

Current Eye Research
|May 24, 2024
PubMed
Abstract

Insights

Microglia inflammation contributes to retinal diseases. This study reveals the Jagged1-Notch1 pathway in M1 microglia disrupts retinal endothelial cell barriers, impacting disease progression.

Area of Science:

  • Ophthalmology
  • Neuroscience
  • Immunology

Background:

  • Microglia-related inflammation is a key factor in retinal disease development.
  • Understanding the role of M1 microglia in retinal barrier integrity is crucial for therapeutic strategies.

Purpose of the Study:

  • To investigate the impact of M1 phenotype microglia on the barrier function of retinal microvascular endothelial cells.
  • To elucidate the underlying mechanisms involving the Jagged1-Notch1 signaling pathway.

Main Methods:

  • Human microglial (HMC3) and retinal microvascular endothelial cells (HRMECs) were used.
  • Quantitative PCR, Western blot, and ELISA assessed M1/M2 markers, cytokines, and Notch signaling.
  • Cellular permeability, tight junction proteins, and apoptosis assays evaluated barrier function.

Main Results:

  • Lipopolysaccharide (LPS) induced M1 polarization in HMC3 cells, increasing pro-inflammatory markers.
  • Conditioned medium from M1 microglia increased HRMEC permeability, reduced tight junction proteins (zonula occludens-1, Occludin), and induced apoptosis.
  • Jagged1 inhibition or Notch1 blockade prevented M1 polarization and preserved HRMEC barrier function.

Conclusions:

  • The Jagged1-Notch1 signaling pathway mediates M1 microglia-induced disruption of the retinal endothelial barrier.
  • This mechanism is implicated in the pathogenesis of retinal diseases.
Keywords:
Jagged1M1 microgliaNotch1apoptosis barrier functiontight junction

More Related Videos

Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo10:50

Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo

Published on: March 26, 2019

7.7K
Generation of Human Microglia to Combine Them with Retinal Organoids for Improved Disease Modeling06:24

Generation of Human Microglia to Combine Them with Retinal Organoids for Improved Disease Modeling

Published on: July 26, 2024

1.2K

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
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...
8.8K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K