Related Experiment Video

Updated: Jul 7, 2026

Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1)
11:19

Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1)

Published on: September 26, 2015

Bradykinin induces matrix metalloproteinase-9 expression and cell migration through a PKC-delta-dependent ERK/Elk-1

Hsi-Lung Hsieh1, Cheng-Ying Wu, Chuen-Mao Yang

  • 1Department of Pharmacology, Chang Gung University, Tao-Yuan, Taiwan.

Glia
|February 2, 2008
PubMed

Insights

Bradykinin (BK) triggers matrix metalloproteinase-9 (MMP-9) expression and cell migration in rat brain astrocytes via a novel signaling pathway involving protein kinase C-delta (PKC-delta) and Elk-1. This study elucidates the molecular mechanisms behind BK-induced MMP-9 upregulation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Matrix metalloproteinase-9 (MMP-9) is implicated in brain inflammation and diseases.
  • Bradykinin (BK) is known to induce proMMP-9 expression in rat brain astrocytes (RBA-1) via MAPKs and NF-kappaB pathways.

Purpose of the Study:

  • To elucidate the molecular mechanisms and physiological roles of BK-induced MMP-9 expression in RBA-1 cells.
  • To identify the specific signaling pathway mediating BK's effects on MMP-9 expression and cell migration.

Main Methods:

  • Investigated the role of the B(2) BK receptor, protein kinase C-delta (PKC-delta), and extracellular signal-regulated kinase 1/2 (ERK1/2) in BK-induced MMP-9 expression.
  • Utilized promoter analysis to identify a crucial Elk-1 binding site in the rat MMP-9 promoter.
  • Examined the recruitment of p300 and histone H4 acetylation at the MMP-9 promoter.

Main Results:

  • BK induced proMMP-9 expression and RBA-1 cell migration via a B(2) BK receptor-activated PKC-delta-dependent pathway.
  • PKC-delta activation led to ERK1/2 phosphorylation and translocation, activating Elk-1.
  • Phospho-Elk-1 bound to a specific site (-511 to -506) on the MMP-9 promoter, inducing transcription.
  • BK promoted p300 recruitment and histone H4 acetylation at the MMP-9 promoter, facilitating gene transcription.

Conclusions:

  • BK-induced MMP-9 gene up-regulation and RBA-1 cell migration are mediated by a PKC-delta/ERK1/2/Elk-1 signaling cascade.
  • The identified Elk-1 binding site and p300-mediated chromatin remodeling are critical for BK's transcriptional control of MMP-9.
  • This pathway highlights a significant mechanism in brain inflammation and astrocyte function.

More Related Videos

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

Related Concept Videos

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...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Overview of Cell-Matrix Interactions01:24

Overview of Cell-Matrix Interactions

The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...