Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β1-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.
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.
['Baszanowska|Weronika|W|', 'Misiura|Magdalena|M|0000-0002-8641-2991', 'Oscilowska|Ilona|I|0000-0002-7934-6973', 'Palka|Jerzy|J|0000-0002-8476-2023', 'Miltyk|Wojciech|W|0000-0001-5150-6093']
D000818:Animals D004150:Dipeptidases D066246:ErbB Receptors D005347:Fibroblasts D005786:Gene Expression Regulation D006801:Humans D019012:Integrin beta1 D051379:Mice D017526:Receptor, IGF Type 1 D015398:Signal Transduction D012867:Skin D014945:Wound Healing
prolidase PEPD EGFR β1-integrin fibroblasts wound healing IGF-1