Tyrosine phosphorylation of EGF-R and PDGF-R proteins during acute cutaneous wound healing process in mice

Mohan L Gope1, Rajalakshmi Gope

  • 1Department of Biotechnology, City College, Bangalore, India.

Insights

Topical application of growth factors like epidermal growth factor (EGF) and platelet-derived growth factors (PDGFs) accelerates wound healing in mice. Increased receptor protein levels and tyrosine phosphorylation, particularly EGF-R and PDGF-R, promote faster skin repair.

Area of Science:

  • Biochemistry
  • Dermatology
  • Regenerative Medicine

Background:

  • Cutaneous wound healing is a complex biological process.
  • Growth factors play a crucial role in regulating tissue repair.
  • Epidermal Growth Factor Receptor (EGF-R) and Platelet-Derived Growth Factor Receptors (PDGF-R) are key mediators.

Purpose of the Study:

  • To investigate the impact of topical EGF and PDGF on EGF-R and PDGF-R levels and activity during wound healing.
  • To determine the correlation between receptor phosphorylation and the rate of cutaneous wound repair.
  • To assess the effect of PDGF-AA alone and in combination with EGF on wound healing.

Main Methods:

  • Acute cutaneous wound model in mice.
  • Analysis of EGF-R and PDGF-R protein expression via Western blotting.
  • Assessment of tyrosine phosphorylation of receptor proteins.
  • Evaluation of wound closure rates.

Main Results:

  • Growth factor treatment led to significantly higher EGF-R and PDGF-R levels by day 1 compared to controls.
  • Tyrosine phosphorylation of mature alpha-PDGF-R and beta-PDGF-R was observed until day 5.
  • PDGF-AA alone did not enhance healing and antagonized EGF-mediated healing, inhibiting receptor phosphorylation.

Conclusions:

  • Rapid and sustained elevation of EGF-R and PDGF-R levels and their tyrosine phosphorylation accelerate wound healing.
  • Optimal receptor activation is critical for effective growth factor-driven tissue repair.
  • Specific PDGF formulations or application timing can interfere with the healing cascade.

Related Concept Videos

Phases of Wound Repair01:28

Phases of Wound Repair

Following injury, the integrity of the injured tissues must be reestablished. For example, in skin tissue, wound repair involves coordination among resident skin cells, blood mononuclear cells, extracellular matrix, growth factors, and cytokines to complete the healing cascade.
Formation of Blood Clot
In case of deep injuries, trauma to blood vessels results in blood loss. In the meantime, phospholipids released from the ruptured endothelial cellular membrane are converted into arachidonic...
Clinical Applications of Epidermal Stem Cells01:19

Clinical Applications of Epidermal Stem Cells

Epidermal stem cells (EpiSCs) are mainly located at the basal layer of the epidermis. These cells repair minor injuries of the skin and replace dead skin cells. However, EpiSCs’ cannot heal severe wounds such as major burns or those from diabetes or hereditary disorders. In such cases, culturing the epidermal stem cells from the patient is possible and has yielded successful treatment options, such as laboratory-grown skin grafts. These grafts are synthesized using a patient’s own EpiSCs...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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...
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 hydroxylase and factor...