Downregulation Of Mir-210 Promotes Sulfur Mustard-Induced Skin Wound Healing

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2019)

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摘要
Sulfur mustard (SM) is a chemical alkylating agent that causes severe vesicating skin injuries. However, the exact mechanisms have not been thoroughly elucidated, limiting the development and optimization of effective therapeutic interventions against SM. MicroRNAs (miRNAs) are small non-coding RNAs with similar to 22 nucleotide lengths, serving as important posttranscriptional gene regulators in cellular activities. Recently, miRNAs, especially miR-210, have been identified to be involved in skin wound healing. Thus, the present study aimed to determine the roles of miR-210 in SM-induced skin injuries in SKH-1 hairless mice. It was confirmed that SM significantly increased expression of miR-210 in skin from 3 days to 14 days post-exposure. miR-210 expressing cells were allocated to the epidermis by in situ hybridization. HIF1 alpha, a key regulator of miR-210, was also increased in line with miR-210 expression. Injections of antago-miR-210 around the wound bed could efficiently lower miR-210 expression levels and promote wound healing. Moreover, antago-miR-210 application promoted keratinocytes migration to the vicinity of wounds. In conclusion, topical SM contamination in the skin could notably upregulate miR-210 expression, while downregulation of miR-210 could accelerate cutaneous wound healing, partially via promoting keratinocyte migration. Present results provide a therapeutic rationale of miR-210 on SM-caused skin injuries.
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关键词
Sulfur mustard, miR-210, keratinocytes migration, skin wound healing
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