Related Experiment Video

Updated: May 17, 2026

A Human Corneal Organ Culture Model of Descemet's Stripping Only with Accelerated Healing Stimulated by Engineered Fibroblast Growth Factor 1
12:36

A Human Corneal Organ Culture Model of Descemet's Stripping Only with Accelerated Healing Stimulated by Engineered Fibroblast Growth Factor 1

Published on: July 22, 2022

Effect of connective tissue growth factor on protein kinase expression and activity in human corneal fibroblasts

Siva S Radhakrishnan1, Timothy D Blalock, Paulette M Robinson

  • 1Institute for Wound Research, University of Florida, Gainesville, Florida 32610-0294, USA.

Investigative Ophthalmology & Visual Science
|November 10, 2012
PubMed
Abstract

Insights

Connective tissue growth factor (CTGF) activates the Ras/MEK/ERK/STAT3 pathway in human corneal fibroblasts. This signaling cascade is essential for CTGF-induced fibroblast proliferation and collagen gel contraction.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Biochemistry

Background:

  • Connective tissue growth factor (CTGF) plays a role in ocular tissue homeostasis and disease.
  • Understanding CTGF signaling in human corneal fibroblasts (HCF) is crucial for developing targeted therapies.

Purpose of the Study:

  • To elucidate the signal transduction pathways activated by CTGF in HCF.
  • To identify key kinases and downstream effectors involved in CTGF-mediated cellular responses.

Main Methods:

  • Protein kinase screens were employed to identify kinases present in quiescent HCF.
  • Phosphorylation levels of key signaling proteins, including ERK1/2 and STAT3, were measured over time following CTGF stimulation.
  • Selective kinase inhibitors were used to assess the role of specific pathways in CTGF-induced fibroblast proliferation and collagen gel contraction.

Main Results:

  • CTGF stimulation rapidly increased the phosphorylation of ERK1/2 (extracellular signal-regulated kinases 1 and 2) and STAT3 (signal transducer and activator of transcription 3).
  • The Ras/MEK/ERK pathway was identified as critical, as its inhibition blocked CTGF-induced HCF proliferation and collagen gel contraction.
  • CTGF also modulated the phosphorylation of other phosphoproteins, including decreases in protein kinases B and C.

Conclusions:

  • The Ras/MEK/ERK/STAT3 signaling pathway is indispensable for mediating CTGF's effects in human corneal fibroblasts.
  • These findings provide a molecular basis for CTGF's role in corneal wound healing and fibrosis.

More Related Videos

In Vitro and In Vivo Models to Study Corneal Endothelial-mesenchymal Transition09:05

In Vitro and In Vivo Models to Study Corneal Endothelial-mesenchymal Transition

Published on: August 20, 2016

Ex Vivo Corneal Organ Culture Model for Wound Healing Studies06:46

Ex Vivo Corneal Organ Culture Model for Wound Healing Studies

Published on: February 15, 2019

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Introduction to Fibroblasts01:09

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
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...
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...
Fibronectins Connect Cells with ECM01:25

Fibronectins Connect Cells with ECM

Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...