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

Byung Cheol Lee, Jisun Song, Arim Lee, Daeho Cho, Tae Sung Kim

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)2185-2193
Number of pages9
JournalInternational journal of molecular medicine
Volume46
Issue number6
DOIs
Publication statusPublished - 2020 Dec

Keywords

  • C‑C motif chemokine ligand 2
  • Erythroid differentiation regulator 1
  • MAPK
  • Wound healing

ASJC Scopus subject areas

  • Genetics

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