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1.
J Cosmet Dermatol ; 23(4): 1178-1186, 2024 Apr.
Article En | MEDLINE | ID: mdl-38251806

BACKGROUND: There is no evidence-based guidance on the use of fractional CO2 laser in the excision of scars. AIM: To explore the effectiveness and safety of fractional CO2 laser in the treatment of keloids. METHODS: In this meta-analysis, we searched the PubMed, Embase, and Cochrane databases from inception to April 2023. We only included studies reporting fractional CO2 laser treatment of keloids. We excluded duplicate published studies, incomplete studies, those with incomplete data, animal experiments, literature reviews, and systematic studies. RESULTS: The pooled results showed that the Vancouver Scar Scale (VSS) parameters of height weighted mean difference (WMD) = -1.10, 95% confidence interval (CI): -1.46 to -0.74), pigmentation (WMD = -0.61, 95% CI: -1.00 to -0.21), and pliability (WMD = -0.90, 95% CI: -1.17 to -0.63) were significantly improved after fractional CO2 laser treatment of keloids. However, vascularity did not significantly change. Additionally, the total VSS was significantly improved after treatment (WMD = -4.01, 95% CI: -6.22 to -1.79). The Patient Scars Assessment Scale was significantly improved after treatment (WMD = -15.31, 95% CI: -18.31 to -12.31). Regarding safety, the incidences of hyperpigmentation, hypopigmentation, pain, telangiectasia, and atrophy were 5%, 0%, 11%, 2% (95% CI: 0%-6%), and 0% (95% CI: 0%-4%), respectively. CONCLUSIONS: Fractional CO2 laser is effective in the treatment of keloids and can effectively improve the height, pigmentation, and pliability of scars, and patients are satisfied with this treatment. Further studies should explore the role of combination therapy.


Cicatrix, Hypertrophic , Keloid , Lasers, Gas , Humans , Keloid/radiotherapy , Keloid/surgery , Keloid/complications , Cicatrix/therapy , Carbon Dioxide , Lasers, Gas/adverse effects , Treatment Outcome , Combined Modality Therapy , Cicatrix, Hypertrophic/pathology
2.
Ital J Dermatol Venerol ; 158(5): 401-407, 2023 Oct.
Article En | MEDLINE | ID: mdl-37916400

Keloids occur after cutaneous injury and can cause distress due to physical appearance and associated symptoms such as pain and pruritus. Keloid-associated pruritus is a common manifestation and has negative impacts on quality of life. The mechanism underlying this type of pruritus is multifactorial and thought to involve small nerve fiber damage, neurogenic inflammation, and a Th2-predominant inflammatory response. Various agents have been shown to reduce keloid pruritus, including intralesional corticosteroids, botulinum toxin A, 5-fluorouracil, and bleomycin. Other treatment modalities such as cryotherapy and hyperbaric oxygen therapy are also effective. Future treatments targeting the mechanisms involved in keloid-associated itch could provide improvements in pruritus and quality of life in these patients, but further studies on the efficacy of these agents are needed.


Keloid , Pruritus , Humans , Cryotherapy/adverse effects , Keloid/complications , Keloid/therapy , Keloid/pathology , Pain/etiology , Pruritus/therapy , Pruritus/complications , Quality of Life , Inflammation
3.
Yonsei Med J ; 64(11): 687-691, 2023 Nov.
Article En | MEDLINE | ID: mdl-37880850

PURPOSE: This study aimed to identify the risk factors associated with the occurrence and prognosis of hypertrophic scarring following thyroidectomy. MATERIALS AND METHODS: A total of 4238 patients who underwent thyroidectomy were included in this study. A multivariable logistic regression model was developed to identify the risk factors for hypertrophic scar development and its prognosis. RESULTS: Our analysis revealed that hypertrophic scar development was associated with younger age [odds ratio (OR)=0.949, p<0.0001], male sex (OR=0.562, p<0.0001), higher body mass index (OR=1.137, p<0.0001), prominent sternocleidomastoid muscles (OR=2.522, p<0.0001), scarring located within 1 cm of the sternal notch (OR=4.345, p<0.0001), and a history of keloid development (OR=2.789, p=0.0031). Additionally, scar location within 1 cm of the sternal notch (beta=4.326, p=0.0429) and a history of keloid development (beta=23.082, p<0.0001) were found to be associated with the prognosis of hypertrophic scarring. CONCLUSION: The findings of this study provide valuable insights into the risk factors associated with hypertrophic scarring following thyroidectomy. Clinicians can use this information to predict the occurrence of hypertrophic scarring and its prognosis, and take preventative measures accordingly.


Cicatrix, Hypertrophic , Keloid , Humans , Male , Body Mass Index , Cicatrix, Hypertrophic/epidemiology , Cicatrix, Hypertrophic/etiology , Cicatrix, Hypertrophic/pathology , Keloid/complications , Keloid/pathology , Prognosis , Risk Factors , Female
5.
F S Sci ; 4(2): 172-180, 2023 05.
Article En | MEDLINE | ID: mdl-37028513

OBJECTIVE: To examine the association between keloids, hypertrophic scars, and uterine fibroid incidence as well as growth. Both keloids and fibroids are fibroproliferative conditions that have been reported to be more prevalent among Blacks than Whites, and they share similar fibrotic tissue structures, including extracellular matrix composition, gene expression, and protein profiles. We hypothesized that women with a history of keloids would have greater uterine fibroid development. DESIGN: A prospective community cohort study (enrollment 2010-2012) with 4 study visits over 5 years to conduct standardized ultrasounds to detect and measure fibroids ≥0.5 cm in diameter, assess the history of keloid and hypertrophic scars, and update covariates. SETTING: Detroit, Michigan area. PATIENTS: A total of 1,610 self-identified Black and/or African American women aged 23-35 years at enrollment without a previous clinical diagnosis of fibroids. EXPOSURE(S): Keloids (raised scars that grow beyond the margins of the original injury) and hypertrophic scars (raised scars that stay within the bounds of the original injury). Because of the difficulties in distinguishing keloids and hypertrophic scars, we separately examined the history of keloids and the history of either keloids or hypertrophic scars (any abnormal scarring) and their associations with fibroid incidence and growth. MAIN OUTCOME MEASURE(S): Fibroid incidence (new fibroid after a fibroid-free ultrasound at enrollment) was assessed using Cox proportional-hazards regression. Fibroid growth was assessed using linear mixed models. The estimates for the change in log volume per 18 months were converted to the estimated percentage difference in volume for scarring vs. no-scarring. Both incidence and growth models were adjusted for time-varying demographic, reproductive, and anthropometric factors. RESULT(S): Of the 1,230 fibroid-free participants, 199 (16%) reported ever having keloids, 578 (47%) reported keloids or hypertrophic scars, and 293 (24%) developed incident fibroids. Neither keloids (adjusted hazard ratio = 1.04; 95% confidence interval: 0.77, 1.40) nor any abnormal scarring (adjusted hazard ratio = 1.10; 95% confidence interval: 0.88, 1.38) were associated with fibroid incidence. Fibroid growth differed little by scarring status. CONCLUSION(S): Despite molecular similarities, self-reported keloid and hypertrophic scars did not show an association with fibroid development. Future research may benefit from the examination of dermatologist-confirmed keloids or hypertrophic scars; however, our data suggest little shared susceptibility for these 2 types of fibrotic conditions.


Cicatrix, Hypertrophic , Keloid , Leiomyoma , Female , Humans , Black or African American , Cicatrix, Hypertrophic/diagnostic imaging , Cicatrix, Hypertrophic/epidemiology , Cicatrix, Hypertrophic/etiology , Cohort Studies , Keloid/diagnostic imaging , Keloid/epidemiology , Keloid/complications , Leiomyoma/diagnostic imaging , Leiomyoma/epidemiology , Prospective Studies , Young Adult , Adult
7.
Skin Therapy Lett ; 27(6): 6-9, 2022 11.
Article En | MEDLINE | ID: mdl-36469561

Acne vulgaris is a troubling skin disease known to have both physiologic and psychological effects on patients. Acne scars, a frequent complication, can further impact patients' quality of life. Scars result from an impairment in the healing process. Acne scars can be categorized as follows: atrophic scars (including ice pick, rolling, boxcar subtypes) and trophic (including hypertrophic and keloid scars), the latter being less common. Though various treatment approaches have been suggested, there is a lack of high-quality evidence on effective, type-specific acne scar approaches. Herein, we aim to review the current evidence for treating various acne scars.


Acne Vulgaris , Keloid , Humans , Quality of Life , Acne Vulgaris/complications , Keloid/complications , Wound Healing , Atrophy/complications , Treatment Outcome
8.
Int J STD AIDS ; 33(13): 1148-1151, 2022 11.
Article En | MEDLINE | ID: mdl-36220799

Pyoderma gangrenosum is a rare neutrophilic inflammatory skin disorder commonly seen over lower limbs. Involvement of penile area is rare. We report this rare case of occurrence of ulcerative type of pyoderma gangrenosum over penis with pustular type elsewhere over the body, healing with keloids in an immunocompetent young man with no systemic associations.


Keloid , Pyoderma Gangrenosum , Male , Humans , Pyoderma Gangrenosum/pathology , Keloid/complications , Keloid/pathology , Penis/pathology , Ulcer/pathology
9.
Cir Pediatr ; 35(4): 207-211, 2022 Oct 01.
Article En, Es | MEDLINE | ID: mdl-36217792

OBJECTIVES: The treatment of keloid scars is based on multiple lines of therapy, with varying levels of efficacy(1), and there is currently no single treatment that guarantees cure and prevents recurrence. In the pediatric population, the treatments used are not standardized, and there is insufficient evidence to support efficacy and complications. The objective of this study was to analyze the patients who required brachytherapy as an adjuvant to surgical resection in recurrent keloid scars. MATERIALS AND METHODS: A retrospective analysis of patients diagnosed with keloids and undergoing adjuvant brachytherapy in our institution was carried out, while assessing efficacy and implementation in our treatment protocol for keloid scarring. RESULTS: After various therapeutic lines, 4 patients aged 9-17 years old with recurrent keloid scars around the ear and eligible for adjuvant brachytherapy - administered after surgical resection, in two sessions - were studied and followed up for up to 18-21 months. CONCLUSIONS: Despite our limited experience in the use of adjuvant brachytherapy, the results obtained to date support its efficacy, as reported in the literature. We therefore consider its inclusion in the treatment of keloid scars that have recurred after other treatments to be appropriate.


OBJETIVOS: El tratamiento de las cicatrices queloideas se basa en múltiples líneas terapéuticas, con diferentes niveles de eficacia(1), sin existir actualmente un tratamiento que garantice su curación y prevenga su recurrencia. En la población pediátrica los tratamientos empleados no están estandarizados y no hay evidencia suficiente que avale su eficacia y sus complicaciones. Este trabajo tiene como objetivo analizar los pacientes que han precisado braquiterapia coadyuvante a la resección quirúrgica en cicatrices queloideas recidivantes. MATERIAL Y METODOS: Análisis retrospectivo de los pacientes diagnosticados en nuestro centro de cicatriz queloidea, en los que se realizó braquiterapia coadyuvante, valorando su eficacia y su implementación en nuestro protocolo de tratamiento de la cicatriz queloidea. RESULTADOS: Se estudiaron 4 pacientes entre 9-17 años con cicatrices queloideas a nivel auricular, recidivantes a varias líneas terapéuticas, que fueron candidatos para el uso de braquiterapia coadyuvante, administrada posterior a la resección quirúrgica, en dos sesiones, se realizó seguimiento hasta 18-21 meses. CONCLUSIONES: A pesar de nuestra limitada experiencia en el uso de la braquiterapia coadyuvante, los resultados obtenidos hasta la fecha avalan su eficacia, de acuerdo con lo publicado en la literatura. Consideramos adecuada su inclusión en el tratamiento de cicatrices queloideas recidivantes a otros tratamientos.


Brachytherapy , Keloid , Adolescent , Brachytherapy/methods , Child , Humans , Keloid/complications , Keloid/radiotherapy , Keloid/surgery , Recurrence , Retrospective Studies , Treatment Outcome
10.
Cir. pediátr ; 35(4): 207-211, Oct. 2022. ilus, tab
Article Es | IBECS | ID: ibc-210864

Objetivos: El tratamiento de las cicatrices queloideas se basa enmúltiples líneas terapéuticas, con diferentes niveles de eficacia (1) , sinexistir actualmente un tratamiento que garantice su curación y prevengasu recurrencia. En la población pediátrica los tratamientos empleados noestán estandarizados y no hay evidencia suficiente que avale su eficaciay sus complicaciones. Este trabajo tiene como objetivo analizar lospacientes que han precisado braquiterapia coadyuvante a la resecciónquirúrgica en cicatrices queloideas recidivantes.Material y métodos: Análisis retrospectivo de los pacientesdiagnosticados en nuestro centro de cicatriz queloidea, en los quese realizó braquiterapia coadyuvante, valorando su eficacia y suimplementación en nuestro protocolo de tratamiento de la cicatrizqueloidea. Resultados: Se estudiaron 4 pacientes entre 9-17 años con cicatricesqueloideas a nivel auricular, recidivantes a varias líneas terapéuticas,que fueron candidatos para el uso de braquiterapia coadyuvante, admi-nistrada posterior a la resección quirúrgica, en dos sesiones, se realizóseguimiento hasta 18-21 meses.Conclusiones: A pesar de nuestra limitada experiencia en el usode la braquiterapia coadyuvante, los resultados obtenidos hasta la fechaavalan su eficacia, de acuerdo con lo publicado en la literatura. Conside-ramos adecuada su inclusión en el tratamiento de cicatrices queloideasrecidivantes a otros tratamientos.(AU)


Objectives: The treatment of keloid scars is based on multiple linesof therapy, with varying levels of efficacy (1) , and there is currently nosingle treatment that guarantees cure and prevents recurrence. In thepediatric population, the treatments used are not standardized, and thereis insufficient evidence to support efficacy and complications. The objective of this study was to analyze the patients who required brachytherapyas an adjuvant to surgical resection in recurrent keloid scars.Materials and methods. A retrospective analysis of patients diagnosed with keloids and undergoing adjuvant brachytherapy in ourinstitution was carried out, while assessing efficacy and implementationin our treatment protocol for keloid scarring.Results: After various therapeutic lines, 4 patients aged 9-17 yearsold with recurrent keloid scars around the ear and eligible for adjuvantbrachytherapy – administered after surgical resection, in two sessions– were studied and followed up for up to 18-21 months.Conclusions: Despite our limited experience in the use of adjuvant brachytherapy, the results obtained to date support its efficacy,as reported in the literature. We therefore consider its inclusion in thetreatment of keloid scars that have recurred after other treatments tobe appropriate.(AU)


Humans , Male , Female , Child , Adolescent , Cicatrix , Brachytherapy , Clinical Protocols , Treatment Outcome , Keloid/complications , Keloid/diagnostic imaging , Keloid/surgery , General Surgery , Pediatrics , Health Systems , Retrospective Studies
12.
HNO ; 70(7): 571-578, 2022 Jul.
Article De | MEDLINE | ID: mdl-35637364

Keloids belong to the group of fibroproliferative diseases and clinically often present with functional and cosmetic impairment of the patient, as well as with pruritus and pain. The pathogenesis of keloids has not been definitively clarified and treatment is often protracted and less than satisfactory. A variety of therapeutic options are available for treatment of keloids; however, the evidence base is small due to studies with low case numbers. Use of multimodal treatment concepts seems to be promising and has shown good results, especially in the treatment of auricular keloids.


Cicatrix, Hypertrophic , Keloid , Cicatrix, Hypertrophic/etiology , Cicatrix, Hypertrophic/therapy , Combined Modality Therapy , Humans , Keloid/complications , Keloid/diagnosis , Keloid/therapy
13.
Clin Otolaryngol ; 47(5): 594-598, 2022 09.
Article En | MEDLINE | ID: mdl-35603527

OBJECTIVES: To assess the efficacy of avoiding mastoid pressure dressing (MPD) on children as a means of preventing discomfort and post-operative pain. DESIGN: A retrospective controlled study. SETTING: All operations were carried out by experienced surgeons using standard techniques, whose custom, not the gravity of any individual case, dictated the use of MPD. PARTICIPANTS: Children who underwent mastoidectomy for inflammatory middle ear diseases at a tertiary centre from 2010 to 2021. MAIN OUTCOME MEASURES: Wound-related complications and Visual Analogue Scale (VAS) pain scores at discharge were compared between children who had an MPD applied following surgery and those who did not. RESULTS: One hundred thirty-five cases were included. The demographic characteristics of the patients and surgical techniques employed were similar for both groups. There were 91 patients in the MPD group and 44 in the non-mastoid dressing (NMPD) group. In the MPD group, five patients developed minor wound dehiscence, eight experienced surgical site infections (SSI), and one patient developed a keloid. In the NMPD group, one patient had an SSI, one patient suffered from a keloid scar, wound dehiscence was observed in one patient, and another one had a local hematoma. Therefore, there were no differences between the groups in relation to post-operative complications (p = .32). Despite these similitudes, the NMPD patients suffered less post-operative pain, as measured by the VAS (p = .02). CONCLUSION: This study shows that no significant benefit is derived from using an MPD after mastoidectomy in children. Surgeons should adhere to principles of appropriate haemostasis and wound closure to prevent post-operative wound complications. Our study supports the abandonment of routine MPD in children following mastoidectomy.


Keloid , Mastoidectomy , Bandages , Child , Humans , Keloid/complications , Pain, Postoperative , Retrospective Studies , Surgical Wound Infection/prevention & control , Wound Healing
15.
Sci Rep ; 11(1): 23669, 2021 12 08.
Article En | MEDLINE | ID: mdl-34880399

Atopic dermatitis (AD) is associated with allergic comorbidities, such as asthma, allergic rhinitis (AR), and allergic contact dermatitis (ACD). The etiology of keloid is largely unknown; however, AD and keloid share inflammatory pathways characterized by T-helper cell 2 cytokines and increased dermal fibroblast activity. The prevalence of keloids has been reported to increase in patients with AD, but it remains controversial. This study aimed to estimate the prevalence of keloids in patients with AD, and compare it with the prevalence of other comorbidities of AD. We assessed the Korean National Health Information Database and medical records including coexisting asthma, AR, and ACD. Single and multiple logistic regression models were created for keloids and each allergic disease. The prevalence of keloids was higher in the AD group than in the control group. Among patients with AD, adolescents and adults had a higher prevalence of keloids than infants and children. The risk of keloids was high with AD alone, and coexisting asthma significantly increased the risk. Similarly, the risk of keloids was higher in AR associated with AD and ACD associated with AD than in AD alone. Thus, among Koreans, patients with AD have a higher risk of keloid development, with coexisting allergic diseases increasing the risk.


Dermatitis, Atopic/complications , Dermatitis, Atopic/epidemiology , Keloid/complications , Keloid/epidemiology , Adolescent , Adult , Aged , Case-Control Studies , Child , Child, Preschool , Comorbidity , Female , Humans , Infant , Male , Middle Aged , Prevalence , Public Health Surveillance , Republic of Korea/epidemiology , Young Adult
16.
Am J Med Genet A ; 185(12): 3675-3682, 2021 12.
Article En | MEDLINE | ID: mdl-34272929

Pathogenic variation in the X-linked gene FLNA causes a wide range of human developmental phenotypes. Loss-of-function is usually male embryonic-lethal, and most commonly results in a neuronal migration disorder in affected females. Gain-of-function variants cause a spectrum of skeletal dysplasias that present with variable additional, often distinctive, soft-tissue anomalies in males and females. Here we present two, unrelated, male individuals with novel, intronic variants in FLNA that are predicted to be pathogenic. Their phenotypes are reminiscent of the gain-of-function spectrum without the skeletal manifestations. Most strikingly, they manifest urethral anomalies, cardiac malformations, and keloid scarring, all commonly encountered features of frontometaphyseal dysplasia. Both variants prevent inclusion of exon 40 into the FLNA transcript, predicting the in-frame deletion of 42 amino acids, however the abundance of FLNA protein was equivalent to that observed in healthy individuals. Loss of these 42 amino acids removes sites that mediate key FLNA functions, including binding of some ligands and phosphorylation. This phenotype further expands the spectrum of the FLNA filaminopathies.


Filamins/genetics , Forehead/abnormalities , Genetic Diseases, X-Linked/genetics , Genetic Predisposition to Disease , Osteochondrodysplasias/genetics , Child , Cicatrix/complications , Cicatrix/genetics , Cicatrix/physiopathology , Exons/genetics , Forehead/physiopathology , Genes, X-Linked , Genetic Diseases, X-Linked/physiopathology , Genetic Variation/genetics , Humans , Infant , Keloid/complications , Keloid/genetics , Keloid/physiopathology , Loss of Function Mutation/genetics , Male , Mutation/genetics , Osteochondrodysplasias/physiopathology , Pedigree , Phenotype , Phosphorylation/genetics , Urethra/abnormalities , Urethra/physiopathology
17.
Sci Rep ; 11(1): 9390, 2021 04 30.
Article En | MEDLINE | ID: mdl-33931723

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998-2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.


Keloid/complications , Neoplasms/pathology , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/etiology , Prognosis , Retrospective Studies , Taiwan/epidemiology , Young Adult
18.
Dermatology ; 237(6): 961-969, 2021.
Article En | MEDLINE | ID: mdl-33789301

BACKGROUND: Keloid scarring is a pathologic proliferation of scar tissue that often causes pruritus, pain, and disfigurement. Keloids can be difficult to treat and have a high risk of recurrence. Recent studies have shown promising results in the treatment of cutaneous metastases with intralesional calcium combined with electroporation (calcium electroporation). As calcium electroporation has shown limited side effects it has advantages when treating benign keloid lesions, and on this indication we performed a phase I study. METHODS: Patients with keloids were treated with at least 1 session of calcium electroporation and followed up for 2 years. Calcium was administered intralesionally (220 mM) followed by the application of eight 100-µs pulses (400 V) using linear-array electrodes and Cliniporator (IGEA, Italy). Treatment efficacy was evaluated clinically (size, shape, erythema), by patient self-assessment (pruritus, pain, other) and assessed histologically. RESULTS: Six patients were included in this small proof of concept study. Treatment was well tolerated, with all patients requesting further treatment. Two out of 6 patients experienced a decrease in keloid thickness over 30%. A mean reduction of 11% was observed in volume size, and a mean flattening of 22% was observed (not statistically significant). Five out of 6 patients reported decreased pain and pruritus. No serious adverse effects or recurrences were observed over a mean follow-up period of 338 days. CONCLUSION: In this first phase I clinical study on calcium electroporation for keloids, treatment was found to be safe with minor side effects. Overall, patients experienced symptom relief, and in some patients keloid thickness was reduced.


Calcium Chloride/therapeutic use , Electrochemotherapy , Keloid/drug therapy , Adult , Erythema/etiology , Erythema/prevention & control , Female , Follow-Up Studies , Humans , Keloid/complications , Keloid/pathology , Male , Middle Aged , Pain/etiology , Pain/prevention & control , Treatment Outcome , Young Adult
20.
Int J Mol Sci ; 21(21)2020 Oct 28.
Article En | MEDLINE | ID: mdl-33126764

Keloid is a representative chronic fibroproliferative condition that occurs after tissue injury. Emerging evidence showed that activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in the pro-inflammatory response in injured tissues. However, the role of NLRP3 inflammasome in keloid progression remains unclear. Notch signaling, which activates NLRP3 inflammasome, is known to contribute to scar formation in keloid, but the cause of enhanced Notch signaling in keloid is not clear. We sought to investigate whether autophagy regulates Notch1 signaling in keloid fibroblasts and determine whether Notch1 signaling might regulate NLRP3 inflammasomes and myofibroblast differentiation. An in vitro model of keloid was established by culturing primary keloid fibroblasts from patients. Expression levels of Notch1, NLRP3 inflammasome proteins, pro-inflammatory cytokines, and myofibroblast markers in keloid fibroblasts were examined and compared with those in normal fibroblasts. Autophagy known to mediate Notch1 degradation was also monitored in fibroblasts. Small interfering RNA (siRNA) targeting Notch1 was used to transfect keloid fibroblasts to further examine the role of Notch signaling in NLRP3 inflammasome activation. Expression levels of Notch1 and NLRP3 inflammasome in keloid fibroblasts increased compared to those in normal fibroblasts. Such increases were accompanied by increased LC3 levels and reduced autophagic flux. Notch1 silencing in keloid fibroblasts by siRNA transfection significantly suppressed increased levels of overall NLRP3 inflammasome complex proteins, NF-kB, and α-smooth muscle actin. Autophagy induction by rapamycin treatment in keloid fibroblasts effectively suppressed expression levels of Notch1 and NLRP3 inflammasome proteins. Decreased autophagy activity in keloid can result in Notch1-mediated myofibroblast activation and NLRP3 inflammasome signaling activation which is critical for chronic inflammation. Collectively, these results identify Notch1 as a novel activator of NLRP3 inflammasome signaling leading to chronic tissue damage and myofibroblast differentiation in keloid progression.


Autophagy , Fibroblasts/pathology , Inflammasomes/metabolism , Inflammation/pathology , Keloid/complications , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Receptor, Notch1/metabolism , Adolescent , Adult , Aged , Chronic Disease , Female , Fibroblasts/immunology , Fibroblasts/metabolism , Humans , Inflammation/etiology , Inflammation/metabolism , Middle Aged , Myofibroblasts/immunology , Myofibroblasts/metabolism , Myofibroblasts/pathology , Signal Transduction , Young Adult
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