细胞外脯氨酸内肽酶（PEPD）通过 EGFR、β-整合素和 IGF-1R 信号通路在创伤成纤维细胞的实验模型中诱导合成代谢过程。

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

机构信息

Department of Medicinal Chemistry, Medical University of Bialystok, Kilińskiego 1, 15-089 Bialystok, Poland.

Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Kilińskiego 1, 15-089 Bialystok, Poland.

出版信息

Int J Mol Sci. 2021 Jan 19;22(2):942. doi: 10.3390/ijms22020942.

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.

在体外培养的成纤维细胞创伤愈合模型中研究了脯氨酰内肽酶（PEPD）作为表皮生长因子受体（EGFR）配体的作用。用 PEPD（1-100 nM）处理细胞，并分析细胞活力、增殖、迁移、胶原蛋白生物合成、PEPD 活性以及 EGFR、胰岛素样生长因子 1（IGF-1）和 β-整合素受体的表达，包括下游信号蛋白。结果发现，PEPD 通过激活 EGFR 下游的 PI3K/Akt/mTOR 信号通路刺激成纤维细胞的增殖和迁移。同时，PEPD 刺激 β-整合素和 IGF-1 受体及其下游的 FAK、Grb2 和 ERK1/2 等蛋白的表达。在 PEPD 处理下，对照和“创伤”成纤维细胞中的胶原蛋白生物合成增加。数据表明，PEPD 诱导的 EGFR 信号可能成为治疗创伤愈合的新尝试。