TY - JOUR
T1 - Accelerated wound healing in diabetic mice by miRNA-497 and its anti-inflammatory activity
AU - Ban, Eunmi
AU - Jeong, Seonghee
AU - Park, Mijung
AU - Kwon, Haejin
AU - Park, Jinyoung
AU - Song, Eun Joo
AU - Kim, Aeri
N1 - 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
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - Diabetic wound healing
KW - IL-1β
KW - IL-6
KW - miRNA-497
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=85074568261&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2019.109613
DO - 10.1016/j.biopha.2019.109613
M3 - Article
C2 - 31707336
AN - SCOPUS:85074568261
SN - 0753-3322
VL - 121
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 109613
ER -