title: Melatonin promotes diabetic wound healing in vitro by regulating keratinocyte activity.
abstract: Diabetic patients are at high risk of developing delayed cutaneous wound healing. Proper keratinocyte proliferation and migration are crucial steps during re-epithelialization. Melatonin (Mel) accelerates wound repair in full-thickness incisional wounds; however, its role in diabetic wound healing is unknown. This study explored the role of Mel in diabetic wound healing in vitro by using high glucose (HG)-cultured keratinocytes. Mel reduced the HG-induced mRNA expression and release of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-8, in keratinocytes. Mel inhibited oxidative stress, as evidenced by reduced production of reactive oxygen species and malondialdehyde and increased activity of superoxide dismutase in HG-stimulated keratinocytes. Mel also inhibited HG-induced nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome activation in keratinocytes. HG-induced reduced migration and proliferation and increased apoptosis of keratinocytes were counteracted by Mel treatment. The pro-proliferative, pro-migratory, and anti-apoptotic effects of Mel on HG-treated keratinocytes were mediated by extracellular signal-regulated kinase signaling pathway. Results collectively suggested that Mel is an alternative therapeutic strategy to ameliorate poor condition for diabetic wound healing by regulating keratinocyte activity.
authors.affiliation: Department of Endocrinology, The Third People's Provincial Hospital of Henan Province Zhengzhou 450000, Henan, China.
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Song
authors.affiliation: Department of Endocrinology, The Third People's Provincial Hospital of Henan Province Zhengzhou 450000, Henan, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Endocrinology, The Third People's Provincial Hospital of Henan Province Zhengzhou 450000, Henan, China.
authors.forename: Haoli
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Endocrinology, The Third People's Provincial Hospital of Henan Province Zhengzhou 450000, Henan, China.
authors.forename: Ruijing
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Endocrinology, The Third People's Provincial Hospital of Henan Province Zhengzhou 450000, Henan, China.
authors.forename: Honghong
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, The Third People's Provincial Hospital of Henan Province Zhengzhou 450000, Henan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, The Third People's Provincial Hospital of Henan Province Zhengzhou 450000, Henan, China.
authors.forename: Xuehui
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Henan Provincial People's Hospital Zhengzhou 450000, Henan, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: School of Life Science and Technology, Shanghai Tech University Shanghai 201210, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Liu
keywords: Diabetic wound healing; chronic inflammation; high glucose; keratinocyte; melatonin; oxidative stress