Accelerated wound healing in diabetic mice by miRNA-497 and its anti-inflammatory activity

Eunmi Ban, Seonghee Jeong, Mijung Park, Haejin Kwon, Jinyoung Park, Eun Joo Song, Aeri Kim

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Diabetic foot ulcers represent one of the major and rising health issues, as the number of diabetic patients is increasing. MicroRNAs (miRNAs) are among various bioactive molecules under investigation for diabetic wound healing. The prolonged pro-inflammatory phase in diabetic wounds partly attributes to its non-healing nature. Therefore, we hypothesized that miRNA-497, known for its regulation of inflammatory responses, would enhance diabetic wound healing. We screened miRNA candidates, including miRNA-497 in the wounded skin of streptozotocin-induced type 1 diabetic mice. The therapeutic potential of miRNA-497 mimic was studied by intradermal injection around the wound in diabetic mice. In addition, the effects of miRNA-497 on pro-inflammatory cytokines were analyzed in the wound lesion of diabetic mice, and in human dermal fibroblasts cells exposed to high glucose and lipopolysaccharide.We found a significant reduction of miRNA-497 expression in the dermal wounds of the diabetic mice relative to normal mice. Intradermal injection of miRNA-497 around the full-thickness dermal wounds in diabetic mice accelerated wound closure effectively compared to the control miRNA. miRNA-497 treatment in vivo and in vitro decreased representative pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Such anti-inflammatory effects of miRNA-497 shed light on its role in accelerating diabetic wound healing. In conclusion, miRNA-497, with its down-regulation activity for pro-inflammatory cytokines, is proposed as a potential therapeutic agent for diabetic wound healing.

Original languageEnglish
Article number109613
JournalBiomedicine and Pharmacotherapy
Volume121
DOIs
StatePublished - Jan 2020

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) ( 2016R1D1A1B03931222 and 2017R1D1A1B03031548 ).

Publisher Copyright:
© 2019 The Authors

Keywords

  • Diabetic wound healing
  • IL-1β
  • IL-6
  • miRNA-497
  • TNF-α

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