Xiamenmycin Attenuates Hypertrophic Scars by Suppressing Local Inflammation and the Effects of Mechanical Stress

Liu, Xiaojin; Xu, Min-Juan; Fan, Si-Teng; Wu, Zheng; Li, Jun; Yang, Xiaomei; Wang, Yahui; Xu, Jun; Zhang, Z.

doi:10.1038/jid.2012.486

Cited by 48 publications

(47 citation statements)

References 49 publications

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“…The results of this observational study suggest that a reduced early inflammatory response is associated with HTS formation. This might be interpreted as being in conflict with the current conception that HTS is related to excessive inflammation . However, previous research of our group also demonstrated signs of decreased inflammation in HTS formation, which supports the findings of the present study …”

Section: Discussionsupporting

confidence: 67%

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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Section: Discussionsupporting

confidence: 67%

Inhibited early immunologic response is associated with hypertrophic scarring

Butzelaar

Schooneman

Soykan

et al. 2016

Experimental Dermatology

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“…Thus, contraction can be regarded as a key pathogenic step in PVR. Cells cultivated in the three-dimensional collagen gel system recapitulated similar morphological changes as observed in vivo 343536. Collagen gel contraction has been used as a model of wound healing process mediated by various cell types, particularly in transdifferentiated RPE cells373839.…”

Section: Discussionmentioning

confidence: 62%

Inhibitory Effect of Bone Morphogenetic Protein 4 in Retinal Pigment Epithelial-Mesenchymal Transition

Yao

Yang

et al. 2016

Sci Rep

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Proliferative vitreoretinopathy (PVR), a serious vision-threatening complication of retinal detachment (RD), is characterized by the formation of contractile fibrotic membranes, in which epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a major event. Recent studies suggest an important role of bone morphogenetic protein 4 (BMP4) in the suppression of fibrosis. In this study, we aimed to investigate the role of BMP4 in the pathological process of PVR, particularly in the EMT of RPE cells. We found that BMP4 and its receptors were co-labelled with cytokeratin and α-SMA positive cells within the PVR membrane. Moreover, the mRNA and protein expression levels of BMP4 were decreased whereas BMP4 receptors ALK2, ALK3 and ALK6 were increased during TGF-β-induced EMT in primary RPE cells. Exogenous BMP4 inhibited TGF-β-induced epithelial marker down-regulation, as well as mesenchymal marker up-regulation at both the mRNA and protein levels in RPE cells. In addition, BMP4 treatment attenuated the TGF-β-induced gel contraction, cell migration and Smad2/3 phosphorylation. However, knockdown of endogenous BMP4 stimulated changes in EMT markers. Our results confirm the hypothesis that BMP4 might inhibit TGF-β-mediated EMT in RPE cells via the Smad2/3 pathway and suppress contraction. This might represent a potential treatment for PVR.

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“…Excessive development of scar‐forming fibroblasts is at the root of pathological scar formation . However, therapeutic options for excessive scarring are limited, and seldom have they been proven to be effective .…”

Section: Discussionmentioning

confidence: 99%