TY - JOUR
T1 - 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
AU - Lee, Byung Cheol
AU - Song, Jisun
AU - Lee, Arim
AU - Cho, Daeho
AU - Kim, Tae Sung
N1 - Funding Information:
This study was supported by the creative Materials discovery Program through the National Research Foundation of Korea (grant no. 2016M3d1A1021387) and the National Research Foundation of Korea (grant no. NRF-2018R1A2B6008434), and a grant from Kine sciences.
Publisher Copyright:
© 2020 Spandidos Publications. All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - C‑C motif chemokine ligand 2
KW - Erythroid differentiation regulator 1
KW - MAPK
KW - Wound healing
UR - http://www.scopus.com/inward/record.url?scp=85094669908&partnerID=8YFLogxK
U2 - 10.3892/ijmm.2020.4762
DO - 10.3892/ijmm.2020.4762
M3 - Article
C2 - 33125115
AN - SCOPUS:85094669908
VL - 46
SP - 2185
EP - 2193
JO - International Journal of Molecular Medicine
JF - International Journal of Molecular Medicine
SN - 1107-3756
IS - 6
ER -