CD26 upregulates proliferation and invasion in keloid fibroblasts through an IGF-1-induced PI3K/AKT/mTOR pathway

Background:Keloid is a fibrotic dermal disease characterized by an abnormal increase in fibroblast proliferation and invasion.These pathological behaviours may be related to the heterogeneity of keloid fibroblasts(KFs);however,because of a lack of effective biomarkers for KFs it is difficult to study the underlying mechanism.Our previous studies revealed that the expansion of CD26+KFs was responsible for increased keloid proliferation and invasion capabilities;the intrinsic relationship and mechanism between CD26 and keloid is therefore worthy of further investigation.The aim of this studywas to explore molecular mechanisms in the process of CD26 upregulated KFs proliferation and invasion abilities,and provide more evidence for CD26 as an effective biomarker of keloid and a new clinical therapeutic target.Methods:Flow cytometry was performed to isolate CD26+/CD26−fibroblasts from KFs and normal fibroblasts.To generate stably silenced KFs for CD26 and insulin-like growth factor-1 receptor(IGF-1R),lentiviral particles encoding shRNA targeting CD26 and IGF-1R were used for transfection.Cell proliferations were analysed by cell counting kit-8 assay and 5-ethynyl-2-deoxyuridine(EdU)incorporation assay.Scratching assay and transwell assay were used to assess cell migration and invasion abilities.To further quantify the regulatory role of CD26 expression in the relevant signalling pathway,RT-qPCR,western blot,ELISA,PI3K activity assay and immunofluorescence were used.Results:Aberrant expression of CD26 in KFs was proven to be associated with increased proliferation and invasion of KFs.Furthermore,the role of the IGF-1/IGF-1 receptor axis was also studied in CD26 and was found to upregulate KF proliferation and invasion.The PI3K/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway was shown to affect CD26-regulated KF proliferation and invasion by increasing phosphorylation levels of S6 kinase and 4E-binding protein.Conclusions:CD26 can be the effective biomarker for KFs,and its expression is closely related to proliferation and invasion in keloids through the IGF-1-induced PI3K/AKT/mTOR pathway.This work provides a novel perspective on the pathological mechanisms affecting KFs and therapeutic strategies against keloids.

Pre-expanded bipedicled visor flap:an ideal option for the reconstruction of upper and lower lip defects postburn in Asian males

Background:Reconstruction of upper and lower lip subunits is a complicated and elusive challenge.For patients affected by defects involving upper and lower lip subunits,a technique able to reconstruct both aesthetic units with matched colour,sufficient contours and similar texture would be ideal.In this study,we present our experience with upper and lower lip reconstruction using the pre-expanded bipedicled visor flap.Methods:From January 2014 to January 2017,12 male patients presenting with defects of the upper and lower lip subunits were treated using this surgical technique.After a period of expansion of the scalp flap of over 6 months,the bipedicled visor flap was raised from both the parietal regions and rotated to resurface the defect.Delay and section of the pedicle were then performed.Results:Twelve male patients with postburn scars aged 22 to 48 years(mean:34 years)were successfully treated with no major complications.The donor site was closed primarily in all cases.Subsequent flap debulking and minor revisions were performed under local anaesthesia between 6 and 12 months postoperatively.Conclusions:The pre-expanded bipedicled visor flap provides an effective and reliable option for upper and lower lip reconstruction with excellent colour and texture.It is feasible to achieve these results simultaneously from a single donor site by using a pre-expanded bipedicled visor flap.

Control of fibrosis and hypertrophic scar formation via glycolysis regulation with IR780

Background:Hypertrophic scars(HS)represent one of the most common clinical challenges due to unsatisfactory therapeutic results.HS formation is associated with the abnormal activation of fibroblasts and their excessive fibrotic behavior.Glycolysis dysregulation has been shown to participate in the incidence and progression of various fibrotic diseases and shows potential as a means of controlling HS formation.This work aimed to discuss the impact of augmented glycolysis on HS and to propose a method for controlling HS formation through glycolysis regulation.Methods:Here,augmented glycolysis was confirmed together with enhanced fibrotic activity in both HS fibroblasts(HFs)and HS tissues,and the suppression of glycolysis also attenuated fibroblast activation.We also introduced IR780,a heptamethine cyanine dye,to regulate glycolysis for the control of HS formation.Results:In vitro,cell studies indicated that IR780 significantly down-regulated glycolysis and suppressed the fibrotic activity of HFs.In vivo,the intralesional injection of IR780 into rabbit HS models led to the downregulation of glycolysis and the control of HS formation.Furthermore,IR780 accumulated preferentially in activated fibroblasts in both in vitro and in vivo studies,and thus specifically downregulated glycolysis and efficiently controlled fibrosis by targeting activated fibroblasts.Conclusions:This work identified a strategy for controlling fibrosis and HS formation from the perspective of glycolysis regulation with IR780 targeting of activated fibroblasts.