Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β 1 -integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts

• Published in: International journal of molecular sciences Vol. 22; no. 2
• Main Authors: Baszanowska, Weronika, Misiura, Magdalena, Oscilowska, Ilona, Palka, Jerzy, Miltyk, Wojciech
• Format: Journal Article
• Language: English
• Published: Switzerland 19.01.2021
• Subjects: Animals; Dipeptidases - genetics; Dipeptidases - pharmacology; ErbB Receptors - genetics; Fibroblasts - drug effects; Gene Expression Regulation - drug effects; Humans; Integrin beta1 - genetics; Mice; Receptor, IGF Type 1 - genetics; Signal Transduction - drug effects; Skin - drug effects; Skin - injuries; Skin - metabolism; Wound Healing - drug effects; Wound Healing - genetics; fibroblasts; wound healing; prolidase; β1-integrin; IGF-1; PEPD; EGFR
• ISSN: 1422-0067

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 β -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 β -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.