Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β1-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.
Weronika BaszanowskaMagdalena MisiuraIlona OściłowskaJerzy A PalkaWojciech MiltykPublished in: International journal of molecular sciences (2021)
The role of prolidase (PEPD) as a ligand of the epidermal growth factor receptor (EGFR) was studied in an experimental model of wound healing in cultured fibroblasts. The cells were treated with PEPD (1-100 nM) and analysis of cell viability, proliferation, migration, collagen biosynthesis, PEPD activity, and the expressions of EGFR, insulin-like growth factor 1 (IGF-1), and β1-integrin receptor including downstream signaling proteins were performed. It has been found that PEPD stimulated proliferation and migration of fibroblasts via activation of the EGFR-downstream PI3K/Akt/mTOR signaling pathway. Simultaneously, PEPD stimulated the expression of β1-integrin and IGF-1 receptors and proteins downstream to these receptors such as FAK, Grb2, and ERK1/2. Collagen biosynthesis was increased in control and "wounded" fibroblasts under PEPD treatment. The data suggest that PEPD-induced EGFR signaling may serve as a new attempt to therapy wound healing.
Keyphrases
- epidermal growth factor receptor
- signaling pathway
- pi k akt
- tyrosine kinase
- wound healing
- small cell lung cancer
- advanced non small cell lung cancer
- induced apoptosis
- cell cycle arrest
- binding protein
- extracellular matrix
- epithelial mesenchymal transition
- cell migration
- growth hormone
- cell proliferation
- poor prognosis
- endothelial cells
- cell adhesion
- cell death
- machine learning
- smoking cessation
- drug induced
- long non coding rna