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Keloid is the abnormal wound healing puzzled by the aggressive growth and high recurrence rate due to its unrevealed key pathogenic mechanism. MicroRNAs contribute to a series of biological processes including epithelial-mesenchymal transition (EMT) and cells stemness involved in fibrotic disease. Here, using microRNAs microarray analysis we found mir-21-5p was significantly up-regulated in keloid epidermis. To investigate the role of miR-21-5p in keloid pathogenesis, we transfected miR-21-5p mimic or inhibitor in keloid keratinocytes and examined the abilities of cell proliferation, apoptosis, migration and invasion, the expressions of EMT-related markers vimentin and E-cadherin and stem-like cells-associated markers CD44 and ALDH1, and the involvement of PTEN and the signaling of AKT and ERK. Our results demonstrated that up-regulation or knockdown of miR-21-5p significantly increased or decreased the migration, invasion and sphere-forming abilities of keloid keratinocytes, and the phenotype of EMT and cells stemness were enhanced or reduced as well. Furthermore, PTEN and p-AKT were shown to participate in the regulation of miR-21-5p on EMT phenotypes and stemness signatures of keloid keratinocytes, which might account for the invasion and recurrence of keloids. This molecular mechanism of miR-21-5p on keloid keratinocytes linked EMT with cells stemness and implicated novel therapeutic targets for keloids.

Several studies have reported on certain aspects of the characteristics of different sites within a keloid lesion, but detailed studies on the keloid dermis at different depths within a keloid lesion are scarce. The aim of this study was to investigate the histology of the keloid dermis at different depths. This study included 19 keloid tissue samples that were collected from 19 patients and 19 normal skin samples, which were harvested from subjects without keloids or hypertrophic scar. Samples were studied by light microscopy using routine hematoxylin and eosin histochemical staining, and immunohistochemistry to detect CD20-positive B-lymphocytes and CD3-positive T-lymphocytes. Sirius Red histochemical staining was used to determine the type of collagen in keloid tissue and normal skin samples. The migratory properties of fibroblasts within the keloid dermis at different depths was compared, using an in vitro migration assay. The findings of this study showed that although the papillary and reticular dermis could be clearly distinguished in normal skin, three tissue layers were identified in the keloid dermis. The superficial dermis of keloid was characterized by active fibroblasts and lymphocytes; the middle dermis contained dense extracellular matrix (ECM) with large numbers fibroblasts, and the deep dermis was poorly cellular and characterized by hyalinized collagen bundles. In the keloid samples, from the superficial to the deep dermis, type I collagen increased and type III collagen decreased, and fibroblasts from the superficial dermis of the keloid were found to migrate more rapidly. In conclusion, the findings of this study showed that different depths within the keloid dermis displayed different biological features. The superficial dermis may initiate keloid formation, in which layer intralesional injection of pharmaceuticals and other treatments should be performed for keloid.

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Human dermal fibrotic disease keloid has been a clinical challenge because of its tumour-like growth and the lack of effective therapy. Dysregulated alternative splicing events have been demonstrated in tumours and fibrosis. In the current study, for the first time, it was demonstrated that the splicing regulator polypyrimidine tract-binding protein (PTB), which plays a pivotal role in tumour proliferation, invasion and metastasis, is overexpressed in keloid tissues and fibroblasts. Additionally, TGF-β1 upregulated the expressions of PTB and its upstream regulator, C-MYC, in keloid fibroblasts. Furthermore, we suppressed PTB using siRNA in keloid fibroblasts and in a keloid xenograft nude mouse model. PTB knockdown significantly slowed the proliferation of keloid fibroblasts and accelerated the regression of transplanted keloid tissues, which was accompanied by a shift in the alternative splicing of USP5 and RTN4. Moreover, when PTB was suppressed, there was a reduction in excessive deposition of FN1 and COL3A1 in transplanted keloid tissues. However, only FN1 was downregulated in keloid fibroblasts that were cultured in media supplemented with TGF-β1. Our study provides evidence for the role of PTB in keloid pathophysiology and offers a novel therapeutic target for keloids. Most importantly, the role TGF-β1 regulation of PTB may provide new insights into the mechanisms underlying inflammatory cytokine-induced fibrosis.

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Background Large-scale maxillocervical scars impair face and neck function and damage appearance. The forehead expanded bilateral superficial temporal pedicled flap is a good treatment strategy for this area; however, the traditional cutaneous pedicled flap damages the temporal hair area. This impairs aesthetics and causes alopecia; furthermore, requires an additional pedicle-cut operation. Methods A retrospective study was performed on 7 patients with large-scale maxillocervical scars from January 2014 to August 2018. Forehead expanders were implanted in the first-stage operation for all patients. After the injection and rest period, patients were treated using the forehead expanded bilateral superficial temporal vascular fascial pedicled flap. Superficial temporal vascular fascia pedicles were carefully harvested. The use of an intralesional or hidden retrotragus incision was determined by the presence of a preauricular scar. Patient satisfaction with postoperative neck activity and the incision scar was evaluated. Results Intralesional and retrovagus incisions were used in 4 and 3 cases, respectively. One flap developed hematoma, which recovered completely after conservative treatment; all other cases had no complications. All flaps healed well. The neck mobility of the patients was significantly improved with no visible scar in the temporal region. Six cases reported being “very satisfied” and one was “relatively satisfied” with their improvement in neck mobility. All cases reported being “very satisfied” with frontotemporal morphology. Conclusions The forehead expanded bilateral superficial temporal vascular fascial pedicled flap is a good choice for patients with large-scale maxillocervical scars. This technique can maintain the aesthetics of temporal hair and reduce patients extra surgical injury.