Keloid Tissue Research Articles

KIAA1429 Promotes Keloid Formation Through the TGF-Β1/Smad Pathway.

Keloid formation is characterized by excessive production of extracellular matrix, leading to dysregulated fibroproliferative collagen response. N6- methyl-adenosine (m6A) modification plays an essential role in this process. Our objective in this study was to explore the mechanism of m6A methyltransferase KIAA1429 in keloid formation. We examined the impact of m6A methyltransferase KIAA1429 on keloid formation using qRT-PCR, Western blot, immunofluorescence, Transwell migration assay, and MeRIP-qPCR. KIAA1429 was downregulated in keloid tissue. Overexpression of KIAA1429 suppressed fibroblast migration and reduced COL1A1 and α-SMA levels. Conversely, the knockdown of KIAA1429 promoted fibroblast migration and COL1A1 and α-SMA levels. Additionally, overexpression of KIAA1429 inhibited the TGF-β1/Smad pathway. Mechanistic experiments suggested that KIAA1429 regulated TGF-β1 m6A modification, maintained TGF-β1 mRNA stability, and participated in the regulation of keloid formation. Furthermore, TGF-β1 could reverse the effects of KIAA1429 overexpression on fibroblast migration and collagen deposition. Taken together, our study suggested that KIAA1429 promoted keloid formation through the TGF-β1/Smad pathway, providing new insights for the treatment of keloid.

NEDD4L Inhibits the Proliferation and Migration of Keloid Fibroblasts by Regulating YY1 Ubiquitination-Mediated Glycolytic Metabolic Reprogramming.

Keloid scarring is a complex fibroproliferative disorder characterised by excessive fibroblast proliferation. Inhibition of cellular glycolysis effectively suppresses the proliferation of keloid fibroblasts (KFs). Neural precursor cell-expressed developmentally downregulated gene 4-like (NEDD4L), a ubiquitin ligase, regulates cell proliferation in different diseases. This study investigated the effects of NEDD4L on glucose metabolism, proliferation and migration in KFs. Primary KFs were isolated from keloid skin tissues obtained from patients with active-stage keloids. Cell transfection was used to upregulate or downregulate NEDD4L and Yin Yang 1 (YY1) in KFs. Protein expression was assessed by immunohistochemistry and western blotting. The viability, proliferative capacity and migration ability of KFs were evaluated using the MTT method and the EdU and wound healing assays, respectively. The regulatory effect of NEDD4L on YY1 ubiquitination was examined by coimmunoprecipitation. The interaction between YY1 and hexokinase 2 (HK2) was confirmed by a dual-luciferase reporter assay. NEDD4L was downregulated, whereas YY1 and HK2 were highly expressed in keloid tissues compared with normal skin. Overexpression of NEDD4L inhibited the proliferation and migration of KFs. NEDD4L promoted YY1 degradation in KFs by inducing its ubiquitination. Upregulation of YY1 induced glucose consumption and lactate production in KFs via the transcriptional regulation of HK2. Increased expression of YY1 reversed the reduced viability, proliferation, and migration of KFs overexpressing NEDD4L. YY1 also reversed the NEDD4L-induced inhibition of glucose consumption and lactate production in KFs. Additionally, an invivo study confirmed the inhibitory roles of NEDD4L overexpression and YY1 knockdown in keloid formation. NEDD4L suppressed the viability, proliferation and migration of KFs by regulating YY1 ubiquitination-mediated glycolysis through HK2. These findings suggest a novel regulatory axis, NEDD4L/YY1/HK2, that mediates glucose metabolism in keloid formation.

Genistein inhibited endocytosis and fibrogenesis in keloid via CTGF signaling pathways

BackgroundThis study aimed to evaluate soy isoflavones' effect and potential use—specifically genistein—in treating human keloid fibroblast cells (KFs) and in a keloid tissue culture model.MethodsTo investigate the effects of genistein on keloid, a wound-healing assay was performed to detect cell migration. Flow cytometry was used to measure apoptosis. Western blotting and immunofluorescence staining were performed to detect the expression of target proteins. KF tissues were isolated, cultured, and divided into the control, silenced connective tissue growth factor (CTGF) proteins, and shNC (negative control) groups.ResultsGenistein suppressed cell proliferation and migration, triggering the cell cycle at the G2/M phase and increasing the expression of p53 dose-dependent in keloids. Genistein inhibited the expression of COL1A1, FN, and CTGF mRNA and protein. Knockdown CTGF reduced the migrated ability in KFs. Genistein also abated TGF-β1-induced keloid fibrosis through the endocytosis model. Separated and cultured the keloid patient’s tissues decreased the cell migration ability by genistein treatment and was time-dose dependent.ConclusionsThis study indicated that genistein-induced p53 undergoes cell cycle arrest via the CTGF pathway-inhibited keloid cultured cells, and genistein suppressed the primary keloid cell migration, suggesting that our research provides a new strategy for developing drugs for treating keloids.

Periostin regulates the activity of keloid fibroblasts by activating the JAK/STAT signaling pathway

A keloid is secondary to skin trauma or has spontaneously manifested as an overgrowth and occurs when the skin heals abnormally after an injury. The main pathological manifestations are abnormal proliferation of keloid fibroblasts (KEL-FIB). This study researched periostin (POSTN) on keloid fibroblasts (KEL-FIB) and the associated mechanism, aiming to provide a reference for the targeted therapy of keloid. We got tissues from Second People’s Hospital of Guangxi Zhuang Autonomous Region between June 2022 and March 2023. POSTN expression was increased in keloid skin tissue and KEL-FIB than normal skin tissue and normal fibroblasts. We collected and inoculated KEL-FIB cells, transfection of si-NC (Silencing of POSTN negative control), si-POSTN (Silencing of POSTN), pcDNA-NC (Overexpression of POSTN negative control), and POSTN (Overexpression of POSTN) (Thermo Fisher Scientific) used Lipofectamine 2000 transfection reagent. Wound closure, cell proliferation viability, migrated cell numbers, and POSTN, p-JAK2, p-STAT3 protein levels were reduced in the si-POSTN group. Wound closure, cell proliferation viability, migrated cell numbers, and POSTN, p-JAK2, p-STAT3 protein levels were elevated in the POSTN group. POSTN protein levels did not changed and wound closure, cell proliferation viability, migrated cell numbers, were reduced in the POSTN+S-Ruxolitinib group. The study results indicated that POSTN promotes cell migration and proliferation by activating the JAK/STAT pathway, promoting KEL-FIB development.

The mechanism of TGF-β mediating BRD4/STAT3 signaling pathway to promote fibroblast proliferation and thus promote keloid progression

ObjectiveThe purpose of this study was to investigate the effect of TGF-β on keloid and its molecular mechanism in fibroblasts. Methods: The difference between normal tissue and keloid tissue can be detected using HE staining. Fibroblasts were treated with TGF-β, and then treated with the BRD4 inhibitor JQ1 and the STAT3 activator Colivelin TFA. Western blot was used to measure the relative protein expression of TGF-β, BRD4, p-STAT3, p-EZH2, C-myc, KLF2, KLF4, α-SMA, and Collagen-I. Immunofluorescence staining was used to measure the relative fluorescence intensity of BRD4, p-STAT3, α-SMA, and Collagen-I. Cell proliferation ability was evaluated by CCK-8 assay and colony formation assay. Results:The expression of TGF-β and BRD4 was significantly higher in keloid tissue compared to normal tissue. TGF-β mediated the BRD4/STAT3 signaling pathway to inhibit p-EZH2 and promote the expression of C-myc, KLF2, KLF4, α-SMA, and Collagen-I. Additionally, TGF-β mediated the BRD4/STAT3 signaling pathway to enhance fibroblast proliferation. Conclusion:TGF-β mediates the BRD4/STAT3 signaling pathway to promote fibroblast proliferation and contribute to the progression of keloid.

Adipose stem cell exosomes promote mitochondrial autophagy through the PI3K/AKT/mTOR pathway to alleviate keloids

BackgroundFibrosis with unrelieved chronic inflammation is an important pathological change in keloids. Mitochondrial autophagy plays a crucial role in reducing inflammation and inhibiting fibrosis. Adipose stem cell-derived exosomes, a product of adipose stem cell paracrine secretion, have pharmacological effects, such as anti-inflammatory and antiapoptotic effects, and mediate autophagy. Therefore, this study aims to investigate the function and mechanism of adipose stem cell exosomes in the treatment of keloids.MethodWe isolated adipose stem cell exosomes under normoxic and hypoxic condition to detect their effects on keloid fibroblast proliferation, migration, and collagen synthesis. Meanwhile, 740YPDGFR (PI3K/AKT activator) was applied to detect the changes in autophagic flow levels and mitochondrial morphology and function in keloid fibroblasts. We constructed a human keloid mouse model by transplanting human keloid tissues into six-week-old (20–22 g; female) BALB/c nude mice, meanwhile, we applied adipose stem cell exosomes to treat the mouse model and observed the retention and effect of ADSC exosomes in vivo.ResultsADSC exosomes can inhibit the PI3K/AKT/mTOR signaling pathway. The exosomes of ADSCs decreased the inflammatory level of KFs, enhanced the interaction between P62 and LC3, and restored the mitochondrial membrane potential. In the human keloid mouse model, ADSC exosomes can exist stably, promote mitochondrial autophagy in keloid tissue, improve mitochondrial morphology, reduce inflammatory reaction and fibrosis. Meanwhile, At the same time, the exosomes derived from hypoxic adipose stem cells have played a more effective role in both in vitro and in vivo experiments.ConclusionsAdipose stem cell exosomes inhibited the PI3K/AKT/mTOR pathway, activated mitochondrial autophagy, and alleviated keloid scars.Graphical

The role of apoptosis, immunogenic cell death, and macrophage polarization in carbon ion radiotherapy for keloids: Targeting the TGF-β1/SMADs signaling pathway

Keloids, characterized by excessive extracellular matrix (ECM) deposition and aberrant fibrous tissue proliferation, present significant therapeutic challenges due to their recalcitrant and recurrent nature. This study explores the efficacy of Carbon Ion Radiotherapy (CIRT) as a novel therapeutic approach for keloids, focusing on its impact on fibroblast proliferation, apoptosis induction, immunogenic cell death (ICD), macrophage polarization, and the TGF-β/SMAD signaling pathway. Utilizing a murine model of keloid formed by subcutaneous injection of zeocin in C57BL/6 mice, we demonstrated that CIRT effectively reduces collagenous fiber synthesis and collagen production in keloid tissues. Further, CIRT was shown to inhibit keloid fibroblast proliferation and to induce apoptosis, as evidenced by increased expression of apoptosis-related proteins and confirmed through flow cytometry and TUNEL assay. Notably, CIRT induced mitochondrial stress, leading to enhanced immunogenicity of cell death, characterized by increased expression of ICD markers and secretion of interferon-γ. Additionally, CIRT promoted a shift from M2 to M1 macrophage polarization, potentially reducing TGF-β release and mitigating ECM deposition. Our findings suggest that CIRT mediates its therapeutic effects through the inhibition of the TGF-β/SMAD signaling pathway, thereby attenuating ECM formation and offering a promising avenue for keloid treatment. This study underscores the potential of CIRT as an innovative strategy for managing keloids, highlighting its multifaceted impact on key cellular processes involved in keloid pathogenesis.

Effectiveness of Core Excision Technique for Keloids: A Systematic Review.

The keloid core excision technique mitigates the risk of wound tension and promotes favorable morphological outcomes. However, whether residual keloid tissue or other factors increase the risk of recurrence remains unclear. This systematic review aimed to evaluate the therapeutic outcomes of core excision techniques for keloids. A systematic literature review was conducted by searching PubMed, Embase, Web of Science Core Collection, and Cochrane Library databases on July 30, 2023. The search terms employed were "keloid," "core excision," "intralesional excision," "intramarginal excision," "rind flap," and "fillet flap." The inclusion criteria for the studies were established in advance and evaluated by multiple investigators. Overall, 20 studies involving 926 keloid cases managed through core excision were included. Adjuvant therapies were used in 19 studies, with radiotherapies and steroid injections emerging as the predominant methods. The recurrence rates ranged from 0% to 28.6%. Residual scar tissue after core excision and complications, such as flap necrosis and hematoma, are the major factors contributing to recurrence. The core excision technique is a surgical treatment of keloids with a low recurrence rate when combined with adjuvant therapies. However, randomized controlled trials and conclusive quantitative studies are necessary to further investigate the effects of the core excision technique on keloids.

IGF1 and CXCR4 Respectively Related With Inhibited M1 Macrophage Polarization in Keloids.

The pathophysiology of keloid remains unclear. Exploring the immune heterogeneity and new biomarkers of keloids can help design new therapeutic targets for keloid treatments and prevention. The authors performed single-cell RNA sequencing analysis and bulk data differential gene expression analysis of public datasets(GSE92566 and GSE163973). They used Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis to identify the function of the differential expressed genes. Besides, the authors performed qt-PCR on keloid tissue and adjacent normal tissues from 3 patients for further verification. M2 macrophage increased in keloid samples than M1 macrophage. The authors identified 2 potential novel biomarkers of keloid, IGF1 and CXCR4, which could inhibit M1 macrophage polarization. The potential mechanism could be inhibiting immune responses and anti-inflammatory activities through INF signaling and E2F targeting. The differential expression of the 2 genes was verified by clinical samples. The authors identified 2 immune signaling molecules associated with keloid formation (IGF1 and CXCR4) and analyzed their potential pathogenic mechanisms.

AURKA Activates FOXO3a to Form a Positive Feedback Loop in the Proliferation and Migration of Keloid Fibroblasts.

Objective: Keloids are benign fibroproliferative disorders with invasive growth exceeding the wound boundary. Aurora kinase A (AURKA) is a serine/threonine kinase highly expressed in various tumors, facilitating tumor growth and invasion. Currently, the role of AURKA in keloid remains unclear. Approach: Fibroblasts were isolated from keloid and normal skin samples. AURKA was evaluated by qPCR, Western blot, and immunohistochemistry. Transcriptome sequencing and dual-luciferase reporter assays were applied to figure out targets of AURKA. Following expression alteration and MLN8237 (an AURKA kinase inhibitor, AKI) treatment, phenotypical experiments were conducted to clarify biological functions of AURKA along with its target, and to probe into the clinical potential of AURKA inhibition. Results: AURKA was upregulated in keloid tissues and fibroblasts. Forkhead box O 3a (FOXO3a) was verified as a downstream of AURKA. Further experiments demonstrated that AURKA transactivated FOXO3a by binding to FOXO3a, while FOXO3a directly transactivated AURKA. Functionally, AURKA and FOXO3a cooperated in enhancing the proliferation and migration of keloid fibroblasts via protein kinase B (AKT) phosphorylation. Although MLN8237 weakened the proliferation and migration in keloid fibroblasts, the transactivation of AURKA on FOXO3a was independent of kinase activity. Innovation: This study reveals that AURKA and FOXO3a compose a transactivation loop in enhancing the proliferative and migrative properties of keloid fibroblasts, and proposes AURKA as a promising target. Conclusion: AURKA/FOXO3a loop promotes the proliferation and migration of keloid fibroblasts via AKT signaling. Despite the anti-keloid effects of AKIs, AURKA acts as a transcription factor independently of kinase activity, deepening our understanding on AKI insensitivity.

SIRT6 Inhibits the Proliferation and Collagen Synthesis of Keloid Fibroblasts through MAPK/ERK Pathway.

Keloid, a fibroproliferative disorder, significantly impacts patients' quality of life, yet effective therapies remain elusive. This study explored the role of silent information regulator 6 (SIRT6) in modulating the proliferation, invasion, and collagen synthesis of keloid fibroblasts. Keloid and normal skin specimens were collected, and fibroblasts were isolated from the keloid tissue. SIRT6 recombinant adenovirus (Ad) was constructed to infect keloid fibroblasts to overexpress SIRT6. This study entails three groups: Control group, adenovirus-Negative Control (Ad-NC) group, and Ad-SIRT6 group. SIRT6 protein and mRNA levels were measured via Western blotting and Quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. Cell viability was determined using 5-ethynyl-2'-deoxyuridine (EdU) assay. Flow cytometry was exploited to measure cell apoptosis. To investigate cell migration, wound healing assay and Transwell assay were employed. Western blotting was also utilized to study the expression levels of apoptotic proteins, collagen deposition-related proteins, and Mitogen-Activated Protein Kinases (MAPK)/extracellular regulated protein kinases (ERK) pathway-related proteins. Compared to the control and Ad-NC groups, the Ad-SIRT6 group exhibited significantly elevated SIRT6 level; diminished cell proliferation, migration and invasion; reduced protein levels of α-smooth muscle actin (α-SMA), collagen I, collagen III, phospho SMAD Family Member 3 (p-Smad3), transforming growth factor-β 1 (TGF-β1), and MAPK/ERK pathway proteins (phospho extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phospho MAP kinase-ERK kinase (p-MEK) and phospho-c-Raf (p-c-Raf)). Treatment with epidermal growth factor (EGF), an MAPK/ERK pathway agonists, reversed the inhibitory effect of SIRT6 on cell activity and inhibited apoptosis in keloid fibroblasts. SIRT6 overexpression in keloid fibroblasts attenuates proliferation, invasion, and collagen synthesis, while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity. This suggests a potential therapeutic target for keloid treatment.

Commensal microbiome dysbiosis elicits interleukin-8 signaling to drive fibrotic skin disease.

Wound healing is an intensely studied topic involved in many relevant pathophysiological processes, including fibrosis. Despite the large interest in fibrosis, the network that is related to commensal microbiota and skin fibrosis remains mysterious. Here, we pay attention to keloid, a classical yet intractable skin fibrotic disease to establish the association between commensal microbiota to scaring tissue. Our histological data reveal the presence of microbiota in the keloids. 16S rRNA sequencing characterizes microbial composition and divergence between the pathological and normal skin tissues. Moreover, the data show elevation of interleukin-8 (IL-8) in both the circulation and keloid tissue, which elicited the collagen accumulation and migratory program of dermal fibroblasts via CXCR1/2 receptor. Our research provides insights into the pathology of human fibrotic diseases, advocating commensal bacteria and IL-8 signaling as useful targets in future interventions of recurrent keloid disease.

Ethyl Pyruvate Decreases Collagen Synthesis and Upregulates MMP Activity in Keloid Fibroblasts and Keloid Spheroids.

Keloids, marked by abnormal cellular proliferation and excessive extracellular matrix (ECM) accumulation, pose significant therapeutic challenges. Ethyl pyruvate (EP), an inhibitor of the high-mobility group box 1 (HMGB1) and TGF-β1 pathways, has emerged as a potential anti-fibrotic agent. Our research evaluated EP's effects on keloid fibroblast (KF) proliferation and ECM production, employing both in vitro cell cultures and ex vivo patient-derived keloid spheroids. We also analyzed the expression levels of ECM components in keloid tissue spheroids treated with EP through immunohistochemistry. Findings revealed that EP treatment impedes the nuclear translocation of HMGB1 and diminishes KF proliferation. Additionally, EP significantly lowered mRNA and protein levels of collagen I and III by attenuating TGF-β1 and pSmad2/3 complex expression in both human dermal fibroblasts and KFs. Moreover, metalloproteinase I (MMP-1) and MMP-3 mRNA levels saw a notable increase following EP administration. In keloid spheroids, EP induced a dose-dependent reduction in ECM component expression. Immunohistochemical and western blot analyses confirmed significant declines in collagen I, collagen III, fibronectin, elastin, TGF-β, AKT, and ERK 1/2 expression levels. These outcomes underscore EP's antifibrotic potential, suggesting its viability as a therapeutic approach for keloids.

MiRSNP rs188493331: A key player in genetic control of microRNA-induced pathway activation in hypertrophic scars and keloids.

Our study aims to delineate the miRSNP-microRNA-gene-pathway interactions in the context of hypertrophic scars (HS) and keloids. We performed a computational biology study involving differential expression analysis to identify genes and their mRNAs in HS and keloid tissues compared to normal skin, identifying key hub genes and enriching their functional roles, comprehensively analyzing microRNA-target genes and related signaling pathways through bioinformatics, identifying MiRSNPs, and constructing a pathway-based network to illustrate miRSNP-miRNA-gene-signaling pathway interactions. Our results revealed a total of 429 hub genes, with a strong enrichment in signaling pathways related to proteoglycans in cancer, focal adhesion, TGF-β, PI3K/Akt, and EGFR tyrosine kinase inhibitor resistance. Particularly noteworthy was the substantial crosstalk between the focal adhesion and PI3K/Akt signaling pathways, making them more susceptible to regulation by microRNAs. We also identified specific miRNAs, including miRNA-1279, miRNA-429, and miRNA-302e, which harbored multiple SNP loci, with miRSNPs rs188493331 and rs78979933 exerting control over a significant number of miRNA target genes. Furthermore, we observed that miRSNP rs188493331 shared a location with microRNA302e, microRNA202a-3p, and microRNA20b-5p, and these three microRNAs collectively targeted the gene LAMA3, which is integral to the focal adhesion signaling pathway. The study successfully unveils the complex interactions between miRSNPs, miRNAs, genes, and signaling pathways, shedding light on the genetic factors contributing to HS and keloid formation.

Kreotoxin A administration inhibits hyperproliferation and inflammation of human ear keloid tissue and keloid-derived fibroblasts by downregulating HIF-1α expression

Keloids represent a prevalent dermal fibroproliferative disorder. They only affect humans and exhibit several tumor characteristics, such as excessive extracellular matrix (ECM) deposition, which usually occurs after skin injury. Kreotoxin type A (KTA) can inhibit the release of acetylcholine, and thereby inhibit the proliferation of keloid fibroblasts and reducing the formation of scars. Thus, KTA could be used as a therapeutic agent for keloids. However, the mechanisms of action of KTA in keloid treatment remain unclear. In this study, we aimed to explore the underlying mechanisms of action of KTA in human keloid treatment using human tissue and a cell-based model. Integrative microarray analysis revealed that hypoxia-inducible factor 1-alpha (HIF-1α) expression was frequently upregulated in hypertrophic scar and keloid tissues, whereas it was downregulated in the KTA-treated samples. Furthermore, KTA addition to keloid-derived fibroblasts (KDFs) reduced the growth rate and viability, induced apoptosis, and decreased inflammation and oxidative stress in KDFs. However, overexpression of HIF-1α restored cell number and survival, decreased apoptosis, and promoted inflammation and oxidative stress in KTA-treated KDFs. Furthermore, KTA treatment reduced the expression of ECM proteins, including vascular endothelial growth factor (VEGF), collagen I and III, whereas HIF-1α overexpression abolished the effects of KTA on KDFs. In conclusion, our findings provide novel insights into the mechanisms of action of KTA as a potential therapeutic agent for keloids via modulating HIF-1α expression.

Exclusive expression of KANK4 promotes myofibroblast mobility in keloid tissues

Keloids are characterized by abnormal wound healing with excessive accumulation of extracellular matrix. Myofibroblasts are the primary contributor to extracellular matrix secretion, playing an essential role in the wound healing process. However, the differences between myofibroblasts involved in keloid formation and normal wound healing remain unclear. To identify the specific characteristics of keloid myofibroblasts, we initially assessed the expression levels of well-established myofibroblast markers, α-smooth muscle actin (α-SMA) and transgelin (TAGLN), in scar and keloid tissues (n = 63 and 51, respectively). Although myofibroblasts were present in significant quantities in keloids and immature scars, they were absent in mature scars. Next, we conducted RNA sequencing using myofibroblast-rich areas from keloids and immature scars to investigate the difference in RNA expression profiles among myofibroblasts. Among significantly upregulated 112 genes, KN motif and ankyrin repeat domains 4 (KANK4) was identified as a specifically upregulated gene in keloids. Immunohistochemical analysis showed that KANK4 protein was expressed in myofibroblasts in keloid tissues; however, it was not expressed in any myofibroblasts in immature scar tissues. Overexpression of KANK4 enhanced cell mobility in keloid myofibroblasts. Our results suggest that the KANK4-mediated increase in myofibroblast mobility contributes to keloid pathogenesis.

Long Non-Coding RNA B3GALT5-AS1 Suppresses Keloid Progression by Regulating the β-Trcp1-Mediated Ubiquitination of HuR.

lncRNA β‑1,3‑galactosyltransferase 5‑AS1 (B3GALT5-AS1) plays a vital regulatory role in colon and gastric cancers. However, the biological functions and regulatory mechanisms of B3GALT5-AS1 in keloid progression remain unknown. This study aims to investigate the molecular mechanisms in the B3GALT5-AS1-regulated keloid proliferation and invasion. Secondary mining of the lncRNA sequencing data from GSE158395 was conducted to screen differentially expressed lncRNAs between keloid and normal tissues. MTT, cell migration and invasion assays were performed to detect the effects of B3GALT5-AS1 on keloid fibroblasts (KFs) proliferation and metastasis. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were also determined to evaluate glycolysis in KFs. RNA pull-down and RNA-protein immunoprecipitation assays were used to confirm the interaction between B3GALT5-AS1 and Hu-Antigen R (HuR). Further ubiquitination and rescue experiments were performed to elucidate the regulatory relationship between B3GALT5-AS1 and HuR. B3GALT5-AS1 was significantly down-regulated in keloid tissues and fibroblasts. B3GALT5-AS1 overexpression significantly inhibited KFs proliferation, glycolysis, invasion, and migration and promoted cell apoptosis, whereas silencing B3GALT5-AS1 inhibited these effects. Moreover, B3GALT5-AS1 binds to HuRand reduces its stability through β-Transducin repeats-containing protein 1 (β-Trcp1)-mediated ubiquitination. Overexpression of HuR reversed the inhibition of B3GALT5-AS1 on cell proliferation, migration, and invasion in KFs, where glycolysis pathway was involved. Our findings illustrate that B3GALT5-AS1 has great effect on inhibition of keloid formation, which provides a potential target for keloid therapy.

Parecoxib decreases cellular growth and Bcl-2 protein levels in primary cultures of keloid fibroblasts.

Keloids seem to overexpress cyclo-oxygenase-2 (COX-2), suggesting a role in its deregulated pathway in inducing an altered epithelial-mesenchymal interaction, which may be responsible for the overgrowth of dermal components resulting in scars or keloid lesions. This study aimed to evaluate the effect of Parecoxib, a COX-2 inhibitor, on cell growth in fibroblast primary cultures obtained from human keloid tissues. Tissue explants were obtained from patients who underwent intralesional excision of untreated keloids; central fractions were isolated from keloid tissues and used for establishing distinct primary cultures. Appropriate aliquots of Parecoxib, a COX-2 inhibitor were diluted to obtain the concentration used in the experimental protocols in vitro (1, 10 or 100 μM). Treatment with Parecoxib (at all concentrations) caused a significant decrease in cellular growth from 24 hours onwards, and with a maximum at 72 hours (P < .02). Moreover, at 72 hours Parecoxib significantly reduced cellular vitality. Parecoxib treatment also induced an increase in fragmented nuclei with a maximum effect at 100 μM and a significant decrease in Bcl-2 and an increase in activated caspase-3 protein levels at 72 hours compared with control untreated cultures. Our findings suggest a potential use of the COX-2 inhibitor, Parecoxib, as the therapy for keloids.

MicroRNAs Associated with Keloids Identified by Microarray Analysis and In Vitro Experiments.

MicroRNAs (miRNAs) play a crucial role in gene regulation and the development of keloid. This research aimed to identify and verify miRNAs associated with keloids by microarray analysis and in vitro experiments, shedding light on seeking for potential therapeutic molecular targets. In this study, the weighted gene co-expression network analysis was performed based on the GSE113620. The key miRNA module most relevant to the keloid was further screened to identify hub miRNAs, and thenhub miRNAs was verified by the microarray analysis and qRT-PCR experiments. Additionally, targeted genes of hub miRNAs were predicted and verified. Gene ontology (GO) analysis and KEGG enrichment analysis were also conducted. Five miRNA modules were divided, and the blue module exhibited the highest correlation with keloids. Then, hsa-miR-127-3p, hsa-miR-214-3p, hsa-miR-155-5p, hsa-miR-409-5p, and hsa-miR-542-5p were identified as the hub miRNAs. Subsequently, the microarray analysis and qRT-PCR results demonstrated that the expression of five miRNAs were upregulated in keloid tissues. The GO analysis revealed that the target genes of these miRNAs were mainly enriched in biological processes including gene transcription, protein phosphorylation and the MAPK (mitogen-activated protein kinase) cascade, and the KEGG pathway enrichment analysis showed that the PI3K-AKT signaling pathway were significantly enriched. In conclusion,these five miRNAs (hsa-miR-127-3p, hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-409-5p, and hsa-miR-542-5p) play vital roles in the pathogenesis of keloid and might be potential therapeutic targets. These miRNAs might regulate genes enriched in gene transcription, protein phosphorylation, the MAPK cascade, and the PI3K-Akt signaling pathway.

Retracted: A Signature of Genes Featuring FGF11 Revealed Aberrant Fibroblast Activation and Immune Infiltration Properties in Keloid Tissue.

[This retracts the article DOI: 10.1155/2022/4452687.].