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GnRH impairs diabetic wound healing through enhanced NETosis

Authors
Lee, YS | Kang, SU  | Lee, MH | Kim, HJ | Han, CH | Won, HR | Park, YU  | Kim, CH
Citation
Cellular & molecular immunology, 17(8). : 856-864, 2019
Journal Title
Cellular & molecular immunology
ISSN
1672-76812042-0226
Abstract
It has been reported that neutrophil extracellular traps (NETs) impair wound healing in diabetes and that inhibiting NET generation (NETosis) improves wound healing in diabetic mice. Gonadotropin-releasing hormone (GnRH) agonists are associated with a greater risk of diabetes. However, the role of GnRH in diabetic wound healing is unclear. We determined whether GnRH-promoted NETosis and induced more severe and delayed diabetic wound healing. A mouse model of diabetes was established using five injections with streptozotocin. Mice with blood glucose levels >250 mg/dL were then used in the experiments. GnRH agonist treatment induced delayed wound healing and increased NETosis at the skin wounds of diabetic mice. In contrast, GnRH antagonist treatment inhibited GnRH agonist-induced delayed wound healing. The expression of NETosis markers PAD4 and citrullinated histone H3 were increased in the GnRH-treated diabetic skin wounds in diabetic mice and patients. In vitro experiments also showed that neutrophils expressed a GnRH receptor and that GnRH agonist treatment increased NETosis markers and promoted phorbol myristate acetate (PMA)-induced NETosis in mouse and human neutrophils. Furthermore, GnRH antagonist treatment suppressed the expression of NETosis markers and PMA-induced NETosis, which were increased by GnRH treatment. These results indicated that GnRH-promoted NETosis and that increased NETosis induced delayed wound healing in diabetic skin wounds. Thus, inhibition of GnRH might be a novel treatment of diabetic foot ulcers.
Keywords
DOI
10.1038/s41423-019-0252-y
PMID
31217526
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
Journal Papers > School of Medicine / Graduate School of Medicine > Orthopedic Surgery
Ajou Authors
강, 성운  |  김, 철호  |  박, 영욱
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