Inhibiting miR-618 Promotes Keratinocytes Proliferation and Migration to Enhance Wound Healing in Mice

Area of Science:

• Molecular Biology
• Wound Healing Research
• Biomedical Science

Background:

• Delayed wound healing is a significant clinical challenge, exacerbated by aging populations and diseases like diabetes.
• MicroRNAs (miRNAs) are critical regulators of biological processes, including wound healing.
• Identifying specific miRNAs involved in impaired healing is crucial for developing new therapies.

Purpose of the Study:

• To investigate the role of miR-618 in the wound healing process.
• To elucidate the molecular mechanisms by which miR-618 affects keratinocyte behavior and inflammation.
• To evaluate the therapeutic potential of targeting miR-618 for accelerating wound closure.

Main Methods:

• Quantitative analysis of miR-618 expression during wound healing.
• In vitro studies on keratinocyte proliferation, migration, and cytokine secretion.
• Mechanistic studies involving target gene identification (Atp11b, Lin7a) and signaling pathway analysis (PI3K-Akt).
• In vivo experiments using miR-618 antagomir in a mouse wound model.

Main Results:

• miR-618 was significantly upregulated during the inflammatory phase of wound healing.
• miR-618 promotes pro-inflammatory cytokine secretion and regulates keratinocyte proliferation and migration.
• miR-618 inhibits the PI3K-Akt signaling pathway by targeting Atp11b, thereby suppressing keratinocyte epithelial-mesenchymal transition (EMT).
• miR-618 also regulates Lin7a gene transcription via the PI3K-Akt pathway.
• In vivo administration of miR-618 antagomir accelerated wound closure in mice.

Conclusions:

• miR-618 plays a detrimental role in wound healing by promoting inflammation and inhibiting keratinocyte functions.
• Targeting miR-618 with antagomirs represents a promising therapeutic strategy for enhancing wound healing.
• miR-618 antagomirs show potential as a novel therapeutic agent for clinical application in wound treatment.