New insights into microRNAs in skin wound healing

Fahs, Fatima; Bi, Xiaoning; Yu, Fei; Zhou, Li; Mi, Qing Sheng

doi:10.1002/iub.1449

Cited by 44 publications

(33 citation statements)

References 70 publications

(86 reference statements)

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“…Recently, epigenetic regulation, such as DNA methylation and histone modification, has been investigated in skin wound healing 18, 19 . DNA methylation mediated by DNA methyltransferases (DNMTs) has an important role in the maintenance of epidermal progenitor self-renewal during embryonic development 20 .…”

Section: Introductionmentioning

confidence: 99%

JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing

Shin

Jeong

et al. 2017

Sci Rep

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It has been shown that epigenetic regulation plays an important role in skin wound healing. We previously found that histone H3K27me3 demethylase JMJD3 regulates inflammation and cell migration in keratinocyte wound healing. In this study, we identified Notch1 as a direct target of JMJD3 and NF-κB in wounded keratinocytes using in vitro cell and in vivo animal models. We found that Notch1 is up-regulated in the wound edge and its expression is dependent on JMJD3 and NF-κB in wounded keratinocytes. We also found that Notch1 activates the expression of RhoU and PLAU gene, which are critical regulators of cell migration. Consistently, depletion or inactivation of Notch1 resulted in decreased filopodia formation, increased focal adhesion and actin stress fiber, leading to reduced keratinocyte migration and skin wound healing. Thus, our findings provide the molecular mechanism involving JMJD3/NF-κB-Notch pathway in keratinocyte wound healing.

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Section: Introductionmentioning

confidence: 99%

JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing

Shin

Jeong

et al. 2017

Sci Rep

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“…Cutaneous wound healing is a complex and interactive process accomplished through inflammatory phase, tissue re‐formation and remodelling phase . Tissue re‐formation occurs through re‐epithelialization and involves keratinocyte migration, proliferation and differentiation at the wounding site . Wound healing is a multistep highly coordinated process, for which many different cellular components a highly coordinated multistep process, involving many different cellular.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Let‐7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2

Zhong

Hou³

et al. 2017

Experimental Dermatology

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Wound healing is a complex process which involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family, let-7b, has been expressed in mammalian skin, but its exact role in keratinocyte migration is still not in knowledge. Here, we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration, while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild-type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. Using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced migration deficiency, which confirms that IGF2BP2 is an important target for let-7b regulation. Our findings suggest that let-7b significantly delayed the re-epithelialization possibly due to reduction of keratinocyte migration and restraints IGF2BP2 during skin wound healing.

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“…Therefore, the differences in increase of protein concentrations during surgery could be caused by alterations on translational level or by miRNA's. These miRNA's can interfere with post‐transcriptional protein expression and have been shown to play a role in wound healing, including the inflammatory phase . Also, it could have been induced by the pre‐operatively increased numbers of M2 macrophages in the HTS group, which inhibit inflammatory mediators .…”

Section: Discussionmentioning

confidence: 99%

“…These miRNA's can interfere with post-transcriptional protein expression and have been shown to play a role in wound healing, including the inflammatory phase. 18 Also, it could have been induced by the pre-operatively increased numbers of M2 macrophages in the HTS group, which inhibit inflammatory mediators. 19 According to Ricketts et al 20 IL-8 promotes tissue remodelling, preventing HTS formation.…”

Section: Discussionmentioning

confidence: 99%

Inhibited early immunologic response is associated with hypertrophic scarring

Butzelaar

Schooneman

Soykan

et al. 2016

Experimental Dermatology

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This study aimed to examine changes in the inflammatory response in early hypertrophic compared to normal wound healing. The immune system is thought to be involved in hypertrophic scar formation. However, the exact mechanism and time of onset of the derailment remain unknown. In a prospective observational study, skin biopsies were taken directly postwounding and 3 hours later from patients who had elective cardiothoracic surgery. The skin biopsies were analysed for mRNA, proteins and cells involved in the early inflammatory phase of wound healing. The endpoint was scar outcome (hypertrophic (HTS) or normal (NTS)) at one year after surgery. There were significant differences between the NTS and HTS groups regarding the fold changes of mRNA expression of P-selectin during surgery. Postoperative skin concentrations of inflammatory proteins IL-6, IL-8 and CCL2 were significantly lower in the HTS compared to the NTS group. Also, a trend of higher pre-operative M2 macrophage numbers was observed in the HTS group. Neutrophil numbers increased equally during surgery in both groups. The increase of P-selectin mRNA in hypertrophic wound healing could affect leucocyte migration. The decreased concentrations of inflammatory proteins in hypertrophic wound healing indicate a reduced inflammatory response, which has consequences for the treatment of hypertrophic scarring during the early inflammatory phase. In a conclusion, alterations of wound healing associated with hypertrophic scarring are visible as early as 3 hours postwounding and include a reduced rather than increased inflammatory protein response.

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New insights into microRNAs in skin wound healing

Cited by 44 publications

References 70 publications

JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing

JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing

MicroRNA Let‐7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2

Inhibited early immunologic response is associated with hypertrophic scarring

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