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Murine Excisional Wound Healing Model and Histological Morphometric Wound Analysis
Published on: August 21, 2020
MicroRNA-132 enhances transition from inflammation to proliferation during wound healing
Abstract:
Wound healing is a complex process that is characterized by an initial inflammatory phase followed by a proliferative phase. This transition is a critical regulatory point; however, the factors that mediate this process are not fully understood. Here, we evaluated microRNAs (miRs) in skin wound healing and characterized the dynamic change of the miRNome in human skin wounds. miR-132 was highly upregulated during the inflammatory phase of wound repair, predominantly expressed in epidermal keratinocytes, and peaked in the subsequent proliferative phase. TGF-β1 and TGF-β2 induced miR-132 expression in keratinocytes, and transcriptome analysis of these cells revealed that miR-132 regulates a large number of immune response- and cell cycle-related genes. In keratinocytes, miR-132 decreased the production of chemokines and the capability to attract leukocytes by suppressing the NF-κB pathway. Conversely, miR-132 increased activity of the STAT3 and ERK pathways, thereby promoting keratinocyte growth. Silencing of the miR-132 target heparin-binding EGF-like growth factor (HB-EGF) phenocopied miR-132 overexpression in keratinocytes. Using mouse and human ex vivo wound models, we found that miR-132 blockade delayed healing, which was accompanied by severe inflammation and deficient keratinocyte proliferation. Together, our results indicate that miR-132 is a critical regulator of skin wound healing that facilitates the transition from the inflammatory to the proliferative phase.
Insights
MicroRNA-132 (miR-132) is crucial for skin wound healing. It promotes the transition from inflammation to proliferation by regulating immune responses and keratinocyte growth.
Area of Science:
- Molecular Biology
- Dermatology
- Wound Healing Research
Background:
- Wound healing involves distinct inflammatory and proliferative phases.
- The molecular mechanisms governing the transition between these phases are not fully elucidated.
- MicroRNAs (miRNAs) are emerging as key regulators in biological processes, including tissue repair.
Purpose of the Study:
- To investigate the role of microRNAs (miRNAs) in human skin wound healing.
- To characterize the dynamic changes in the miRNome during the wound healing process.
- To determine the specific function of miR-132 in regulating the transition from inflammation to proliferation.
Main Methods:
- Profiling of microRNA expression in human skin wounds.
- In vitro studies using keratinocytes stimulated with TGF-β1 and TGF-β2.
- Transcriptome analysis to identify miR-132 targets.
- Inhibition of miR-132 in mouse and human ex vivo wound models.
Main Results:
- miR-132 expression is upregulated during wound inflammation, peaking in the proliferative phase.
- miR-132 suppresses leukocyte attraction via the NF-κB pathway but promotes keratinocyte proliferation via STAT3 and ERK pathways.
- HB-EGF was identified as a functional target of miR-132.
- Blocking miR-132 in wound models resulted in delayed healing, persistent inflammation, and impaired keratinocyte proliferation.
Conclusions:
- miR-132 is a critical regulator of skin wound healing.
- miR-132 facilitates the transition from the inflammatory to the proliferative phase.
- Targeting miR-132 presents a potential therapeutic strategy for enhancing wound repair.
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