Erythroid differentiation regulator 1 promotes wound healing by inducing the production of C‑C motif chemokine ligand 2 via the activation of MAP kinases in vitro and in vivo

Abstract

The erythroid differentiation regulator 1 (Erdr1) protein has been studied for its role in various inflammatory skin diseases, including skin cancer, actinic keratosis and psoriasis. However, the therapeutic effects of Erdr1 on wound repair and its underlying mechanisms remain unknown. The present study aimed to investigate the effects of Erdr1 on wound healing in vitro and in vivo . The results demonstrated that treatment with recombinant Erdr1 enhanced wound healing in vivo and in vitro . In addition, Erdr1 increased the proliferation and migration of human dermal fibroblasts (HDFs). Notably, Erdr1 significantly induced the production of the chemoattractant C-C motif chemokine ligand 2 (CCL2) and recruited immune cells involved in wound healing. Treatment with recombinant Erdr1 induced the activation of the ERK1/1, p38 and JNK1/2 mitogen-activated protein (MAP) kinases. Treatment with specific inhibitors for MAP kinase inhibitors markedly suppressed cell proliferation and migration, and inhibited the production of CCL2 in HDFs. Furthermore, the inhibition of CCL2 with a neutralizing antibody significantly suppressed the recombinant Erdr1-induced proliferation and migration of HDFs. The wound healing activity of Erdr1 was comparable to that of epidermal growth factor. Taken together, these results demonstrated that Erdr1 promoted the proliferation and migration of HDFs and exhibited potent wound healing properties mediated by CCL2. Therefore, the results of the present study suggested that Erdr1 may be a potential therapeutic target for promoting wound healing.

Human fetal dermal fibroblast-myeloid cell diversity is characterized by dominance of pro-healing Annexin1-FPR1 signaling

“… 106 , 107 A significant role of CCL2 in achieving wound closure is well documented. 108 , 109 , 110 In summary, a comprehensive bioinformatic analysis of scRNA-seq data from human fetal and adult tissues identifies Annexin1-FPR1 signaling as a major communication pathway responsible for a functional relationship between myeloid cells and fibroblasts during tissue repair and regeneration.…”

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