The biodistribution of triamcinolone acetonide injections in severe keloids: an exploratory three-dimensional fluorescent cryomicrotome study.

Intralesional corticosteroid injections are a first-line treatment for keloids; yet clinical treatment results are highly variable and often suboptimal. Variation in triamcinolone acetonide (TAC) biodistribution may be an important reason for the variable effects of TAC treatment in keloids. In this exploratory study we investigated the biodistribution of TAC in keloids and normal skin using different drug delivery techniques. Fluorescent-labeled TAC suspension was administered into keloids and normal skin with a hypodermic needle and an electronic pneumatic jet injector. TAC biodistribution was represented by the fluorescent TAC volume and 3D biodistribution shape of TAC, using a 3D-Fluorescence-Imaging Cryomicrotome System. Twenty-one keloid and nine normal skin samples were analyzed. With needle injections, the mean fluorescent TAC volumes were 990 µl ± 479 in keloids and 872 µl ± 227 in normal skin. With the jet injector, the mean fluorescent TAC volumes were 401 µl ± 252 in keloids and 249 µl ± 67 in normal skin. 3D biodistribution shapes of TAC were highly variable in keloids and normal skin. In conclusion, TAC biodistribution in keloids is highly variable for both needle and jet injection. This may partly explain the variable treatment effects of intralesional TAC in keloids. Future research is needed to confirm this preliminary finding and to optimize drug delivery in keloids.

STAT3-induced lncRNA GNAS-AS1 accelerates keloid formation by mediating the miR-196a-5p/CXCL12/STAT3 axis in a feedback loop.

Keloids are pathological scar tissue resulting from skin trauma or spontaneous formation, often accompanied by itching and pain. Although GNAS antisense RNA 1 (GNAS-AS1) shows abnormal upregulation in keloids, the underlying molecular mechanism is unclear. The levels of genes and proteins in clinical tissues from patients with keloids and human keloid fibroblasts (HKFs) were measured using quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay. The features of HKFs, including proliferation and migration, were evaluated using cell counting kit 8 and a wound healing assay. The colocalization of GNAS-AS1 and miR-196a-5p in HKFs was measured using fluorescence in situ hybridization. The relationships among GNAS-AS1, miR-196a-5p and C-X-C motif chemokine ligand 12 (CXCL12) in samples from patients with keloids were analysed by Pearson correlation analysis. Gene interactions were validated by chromatin immunoprecipitation and luciferase reporter assays. GNAS-AS1 and CXCL12 expression were upregulated and miR-196a-5p expression was downregulated in clinical tissues from patients with keloids. GNAS-AS1 knockdown inhibited proliferation, migration, and extracellular matrix (ECM) accumulation of HKFs, all of which were reversed by miR-196a-5p downregulation. Signal transducer and activator of transcription 3 (STAT3) induced GNAS-AS1 transcription through GNAS-AS1 promoter interaction, and niclosamide, a STAT3 inhibitor, decreased GNAS-AS1 expression. GNAS-AS1 positively regulated CXCL12 by sponging miR-196-5p. Furthermore, CXCL12 knockdown restrained STAT3 phosphorylation in HKFs. Our findings revealed a feedback loop of STAT3/GNAS-AS1/miR-196a-5p/CXCL12/STAT3 that promoted HKF proliferation, migration and ECM accumulation and affected keloid progression.

A Novel Method for Patients With Ear Keloid: Enucleation and Fat Grafting.

BACKGROUND: Keloid is a dermal fibroproliferative disease unique to humans. Due to the ambiguity in its pathophysiology and the frequent recurrence of keloid, there is no clear consensus on the treatment of keloid and there are many treatment methods defined. In order to benefit from the positive effects of fat grafting on pathological scars, we applied fat grafting to patients who underwent keloid enucleation. METHODS: Fifteen ear keloid patients included in the study. All patients underwent the same surgical procedure by the same surgeon. Routine follow-ups and examinations were performed to evaluate the results and in addition, the Patient and Observer Scar Assessment Scale (POSAS) survey was used. RESULTS: In the study, 15 patients were followed for a median (IQR) period of 21 (13-28) months. No recurrence was observed in any patient during follow-up, which occurred for a median of 21 (13-28) months. In the questionnaire filled out by the patients, the preoperative median value was found to be 48 (IQR: 12), whereas the postoperative median value was found to be 14 (IQR: 8). According to the patients, there was a statistically significant ( P < 0.05) positive improvement after surgery. CONCLUSIONS: Historically, surgical procedures were avoided because the surgical recurrence rate was very high, but today, recurrence rates are decreasing with combined treatments. These treatment combinations may require more than one intervention and require frequent clinical follow-ups. With our technique of fat grafting after enucleation, the treatment was completed with a single operation and no additional intervention was required.

Advances in laser therapies for the scar. / ç˜¢ç—•çš„æ¿€å ‰æ²»ç–—è¿›å±•.

Scars are classified into 5 types: Superficial scars, hypertrophic scars, atrophic scars, depressed scars, and keloid. These types are primarily characterized by abnormal production of fibroblasts and collagen, as well as the disorderly arrangement of connective tissue. Laser treatment for scars involves the coordinated activation of various signaling pathways and cytokines. However, the exact pathological mechanism for scar formation remains unclear, leading to a lack of radical treatment. Recently, laser treatment has gained popularity as a new minimally invasive approach for scar treatment. The emergence of new theories such as fractional, picosecond laser, and laser-assisted drug delivery has led to continuous advance in laser treatment. Up to now, it has been developed numerous novel treatments, including combined with drug, physical, and other treatments, which have shown superior therapeutic effects. In order to optimize laser treatment in the future, it is crucial to combine new materials with postoperative care. This will help clinicians develop more comprehensive treatment strategies. Therefore, it is important to explore treatment options that have broader applicability.

No Association of Polymorphisms in the Genes Encoding Interleukin-6 and Interleukin-6 Receptor Subunit Alpha with the Risk of Keloids in Polish Patients.

A keloid is a benign fibroproliferative hypertrophy of scar tissue that extends outside the original wound and invades adjacent healthy skin. Keloid formation is thought to be a complex process including overactivity of the interleukin-6 signaling pathway and genetic susceptibility. The aim of the study was to investigate possible associations between rs1800797, rs1800796, and rs1800795 polymorphisms in the promoter of the IL6 gene encoding interleukin-6 and the rs2228145 polymorphism in the IL6R gene encoding the interleukin-6 receptor subunit alpha with the predisposition to keloids in Polish patients. The genetic polymorphisms were identified either using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or sequencing of samples of genomic DNA extracted from blood leukocytes of 86 adult patients with keloids and 100 newborns comprising a control group. No significant differences in the distributions of IL6 or IL6R alleles or genotypes were found between keloid patients and newborn controls. There were also no significant differences between both groups in the distribution of IL6 haplotypes. The IL6 rs1800797, rs1800796 and rs1800795 and IL6R rs2228145 polymorphisms were not found to predispose individuals in the study group to keloids. IL6 promoter haplotypes were not found to be associated with a higher risk of keloids in the studied group.

Pharmacotherapy for Keloids and Hypertrophic Scars.

Keloids (KD) and hypertrophic scars (HTS), which are quite raised and pigmented and have increased vascularization and cellularity, are formed due to the impaired healing process of cutaneous injuries in some individuals having family history and genetic factors. These scars decrease the quality of life (QOL) of patients greatly, due to the pain, itching, contracture, cosmetic problems, and so on, depending on the location of the scars. Treatment/prevention that will satisfy patients' QOL is still under development. In this article, we review pharmacotherapy for treating KD and HTS, including the prevention of postsurgical recurrence (especially KD). Pharmacotherapy involves monotherapy using a single drug and combination pharmacotherapy using multiple drugs, where drugs are administered orally, topically and/or through intralesional injection. In addition, pharmacotherapy for KD/HTS is sometimes combined with surgical excision and/or with physical therapy such as cryotherapy, laser therapy, radiotherapy including brachytherapy, and silicone gel/sheeting. The results regarding the clinical effectiveness of each mono-pharmacotherapy for KD/HTS are not always consistent but rather scattered among researchers. Multimodal combination pharmacotherapy that targets multiple sites simultaneously is more effective than mono-pharmacotherapy. The literature was searched using PubMed, Google Scholar, and Online search engines.

[Clinical study of ear keloids with surgical excision and intraoperative low-energy X-ray irradiation therapy].

Objective:To explore the clinical efficacy of surgical excision combined with low-energy X-ray irradiation in the treatment of ear keloids. Methods:Clinical data of 32 cases of ear keloid lesions that received surgical treatment alone or surgery combined with radiotherapy from March 2019 to November 2022 in the Department of Otorhinolaryngology Head and Neck Surgery of the Tianjin First Central Hospital were retrospectively analyzed. Among them, 10 cases received radiotherapy and 22 cases did not receive radiotherapy. The radiotherapy group received irradiation with a large divided dose of 50 kV low-energy X-rays. The mode of fractionation radiotherapy was as follows: the first was 10 Gy of intraoperative radiation therapy and the second was 8 Gy on the 3rd postoperative day for a total of 18 Gy. The local efficacy and skin radiation reaction were observed at a follow-up of 8-52 months. Results:The median follow-up was 26 months, and as of the date of the last follow-up, 9 cases were cured and 1 case was ineffective in the radiotherapy group, with an effective rate of 90.0%, while 9 cases were cured and 13 cases were ineffective in the no-radiotherapy group, with an effective rate of 40.9%. The recurrence of ear keloids was not related to the side, site, or etiology of the patient's onset（P>0.05）. Recurrence was related to whether or not the patients received radiotherapy（χ²=4.885, P<0.05）, and the recurrence rate in the radiotherapy group（10.0%） was significantly lower than that in the non-radiotherapy group（59.1%）. Conclusion:Surgical excision combined with low-energy X-ray irradiation therapy is an effective method of treating keloids in the ear, especially with intraoperative radiation therapy can achieve more satisfactory results.

[Research advances on the role of aerobic glycolysis in skin fibrosis diseases].

Skin fibrosis diseases mainly include hypertrophic scar, keloid, and systemic sclerosis, etc. The main pathological features are excessive activation of fibroblasts and abnormal deposition of extracellular matrix. In recent years, studies have shown that aerobic glycolysis is closely related to the occurrence and development of skin fibrosis diseases. Drugs targeting aerobic glycolysis has provided new ideas for skin anti-fibrosis treatment. This article reviews the role of enzymes and products related to aerobic glycolysis in the occurrence and development of skin fibrosis diseases and the drugs targeting aerobic glycolysis for the treatment of skin fibrosis diseases.

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.

The effects of systemic diseases, genetic disorders and lifestyle on keloids.

Keloid are a fibroproliferative disorder caused by abnormal healing of skin, specifically reticular dermis, when subjected to pathological or inflammatory scars demonstrating redness, elevation above the skin surface, extension beyond the original wound margins and resulting in an unappealing cosmetic appearance. The severity of keloids and risk of developing keloids scars are subjected to elevation by other contributing factors such as systemic diseases, general health conditions, genetic disorders, lifestyle and natural environment. In particular, recently, daily physical work interpreted into mechanical force as well as the interplay between mechanical factors such as stress, strain and stiffness have been reported to strongly modulate the cellular behaviour of keloid formation, affect their location and shape in keloids. Herein, we review the extensive literature on the effects of these factors on keloids and the contributing predisposing mechanisms. Early understanding of these participating factors and their effects in developing keloids may raise the patient awareness in preventing keloids incidence and controlling its severity. Moreover, further studies into their association with keloids as well as considering strategies to control such factors may help clinicians to prevent keloids and widen the therapeutic options.

Effective keloid management using a combinatorial continuous-wave and repeat fractionated ablative CO2 laser regimen.

BACKGROUND: Keloids are benign proliferative scars that form as a result of dysregulated growth and collagen deposition in response to cutaneous injury. Laser therapies have emerged as promising options for the treatment of keloids, with performance varying by laser type and lesion characteristics. PURPOSE: To assess the combined continuous wave and repetitive fractionated CO2 laser treatment of keloids. METHODS: A retrospective chart review of 22 cases of keloid scars treated with combined CO2 laser modes. A single session of continuous wave followed by five sessions of fractional delivery. Efficacy was assessed using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale. The Numeric Rating Scale was used to assess patient satisfaction and pain. RESULTS: Most patients were female (77.3%) with skin type IV (72.7%), age was 24.3 ± 9.3 years, most keloids were located on the earlobe (56.5%) or arm or hand (17.4%), size ranged from 5 to 10 cm, and time since injury ranged from 3 months to 35 years. No serious adverse events were reported. At 6 months, significant improvements from baseline occurred in all characteristics, scar color (4.8 ± 2.8 to 1.9 ± 1.1), rigidity (5.0 ± 2.8 vs. 5.4 ± 2.8), thickness (5.4 ± 2.8 vs. 2.0 ± 1.1), and irregularity (5.9 ± 2.4 vs. 1.9 ± 0.9). The Vancouver scores followed a similar trend. Patient-rated overall improvement from 37 ± 17.6 at baseline to 16.1 ± 8.5 at 6 months, and improvement in associated pain and pruritus. CONCLUSION: Combination of two ablative laser delivery modes within a single laser platform provided for effective and safe keloid management and left patients highly satisfied.

Revealing the pathogenesis of keloids based on the status: Active vs inactive.

Recently, the pathomechanisms of keloids have been extensively researched using transcriptomic analysis, but most studies did not consider the activity of keloids. We aimed to profile the transcriptomics of keloids according to their clinical activity and location within the keloid lesion, compared with normal and mature scars. Tissue samples were collected (keloid based on its activity (active and inactive), mature scar from keloid patients and normal scar (NS) from non-keloid patients). To reduce possible bias, all keloids assessed in this study had no treatment history and their location was limited to the upper chest or back. Multiomics assessment was performed by using single-cell RNA sequencing and multiplex immunofluorescence. Increased mesenchymal fibroblasts (FBs) was the main feature in keloid patients. Noticeably, the proportion of pro-inflammatory FBs was significantly increased in active keloids compared to inactive ones. To explore the nature of proinflammatory FBs, trajectory analysis was conducted and CCN family associated with mechanical stretch exhibited higher expression in active keloids. For vascular endothelial cells (VECs), the proportion of tip and immature cells increased in keloids compared to NS, especially at the periphery of active keloids. Also, keloid VECs highly expressed genes with characteristics of mesenchymal activation compared to NS, especially those from the active keloid center. Multiomics analysis demonstrated the distinct expression profile of active keloids. Clinically, these findings may provide the future appropriate directions for development of treatment modalities of keloids. Prevention of keloids could be possible by the suppression of mesenchymal activation between FBs and VECs and modulation of proinflammatory FBs may be the key to the control of active keloids.

MEG3 shuttled by exosomes released from human bone marrow mesenchymal stem cells promotes TP53 stability to regulate MCM5 transcription in keloid fibroblasts.

BACKGROUND: Despite the interest in mesenchymal stem cells (MSC), their potential to treat abnormal scarring, especially keloids, is yet to be described. The present study aimed to investigate the therapeutic potential of exosomes derived from human bone marrow MSCs (hBMSC-Exos) in alleviating keloid formation. METHODS: Exosomes were isolated from hBMSC, and keloid fibroblasts (KFs) were treated with hBMSC-Exos. Cell counting kit-8, wound healing, transwell invasion, immunofluorescence, and western blot assays were conducted to study the malignant phenotype of KFs. Mice were induced with keloids and treated with hBMSC-Exos. The effect of hBMSC-Exos on keloid formation in vivo was evaluated by hematoxylin and eosin staining, Masson staining, immunohistochemistry, and western blotting. The GSE182192 dataset was screened for differentially expressed long non-coding RNA during keloid formation. Next, maternally expressed gene 3 (MEG3) was knocked down in hBMSC to obtain hBMSC-Exossh-MEG3. The molecular mechanism of MEG3 was investigated by bioinformatic screening, and the relationship between MEG3 and TP53 or MCM5 was verified. RESULTS: hBMSC-Exos inhibited the malignant proliferation, migration, and invasion of KFs at same time as promoting their apoptosis, Moreover, hBMSC-Exos reduced the expression of fibrosis- and collagen-related proteins in the cells and the formation of keloids caused by KFs. The reduction in MEG3 enrichment in hBMSC-Exos weakened the inhibitory effect of hBMSC-Exos on KF activity. hBMSC-Exos delivered MEG3 to promote MCM5 transcription by TP53 in KFs. Overexpression of MCM5 in KFs reversed the effects of hBMSC-Exossh-MEG3, leading to reduced KF activity. CONCLUSIONS: hBMSC-Exos delivered MEG3 to promote the protein stability of TP53, thereby activating MCM5 and promoting KF activity.

The clinical efficacy of single-hole punch excision combined with intralesional steroid injection for nodular keloid treatment: a self-controlled trial.

There are many methods to treat keloid, including various excision operations, laser, injection and radiotherapy. However, few studies have explored the effectiveness of single-hole punch excision in keloid treatment. This study aimed to investigate the efficacy and safety of lateral punch excision combined with intralesional steroid injection for keloid treatment through self-control trial. In this self-controlled trial, 50 patients meet the diagnosis of nodular keloid, and try to choose left-right symmetrical control, one skin lesion in the control group (50 skin lesionsin total) and the other in the observation group (50 skin lesions in total).The keloids in the treatment group were initially treated with punch excision combined with intralesional steroid injection, followed by injection treatment alone. Keloids in the control group received intralesional steroid injection alone. The Vancouver Scar Scale (VSS) of the keloid before and after the punch excision was evaluated; the keloid scores at different time points and the number of injection treatments required in both groups were compared, and adverse reactions were observed. The effective rate of the observation group was 86.0%, which was significantly higher than that of the control group (66.0%), and the recurrence rate of 22% was lower than that of the control group (χ2 = 4.141,63417), all of which were statistically significant (all P < 0.05). At the end of treatment, the VSS and total injection times in the observation group were significantly lower than those in the control group (t = 5.900,3.361), with statistical significance (P < 0.01). The combination of single-hole punch excision and intralesional steroid injection is an effective method to treat multiple nodular keloids, shortening the treatment course of tralesional steroid injection without obvious adverse reactions.

Dermatofibrosarcoma protuberans of the breast.

Dermatofibrosarcoma protuberans (DFSP) of the breast is an infrequent soft tissue sarcoma that usually affects young to middle-aged women. Our case report describes a unique occurrence of DFSP of the breast in an adolescent girl, which was initially being managed as a keloid for 2 years under dermatology despite being refractory to treatment. Once the diagnosis of DFSP was confirmed through punch biopsy, our patient underwent surgical excision of the lesion under general anaesthesia. Our patient was at an increased risk of damage to the ductal system due to proximity of the lesion to the nipple-areolar complex, warranting the need for early recognition and treatment. As demonstrated by our case, DFSP of the breast can be difficult to diagnose since it resembles a range of benign and malignant pathologies of the breast.

A Single-Institution Review of the Use of Radiation in the Adjuvant and Definitive Management of Keloids.

AIMS: Many individuals suffer from keloids that are refractory to standard treatment modalities, including surgical excision alone. Radiation therapy can be used to reduce the risk of recurrent keloids post-operatively, as well as be used as primary treatment for keloids not amenable to surgical resection. The purpose of this study was to review our institutional experience of radiation therapy for keloid management. MATERIALS AND METHODS: A retrospective review of patients treated with radiation therapy for keloids between 2014 and 2020 at our institution was performed. RESULTS: A total of 70 keloids in 41 patients were treated. For the 55 keloids treated with post-operative radiation therapy (16Gy delivered in 2 fractions), 82.5% (33/40) of evaluable lesions did not recur. Among the 15 keloids treated with definitive radiation therapy (24Gy delivered in 3 fractions), 78.6% (11/14) of evaluable keloids showed complete flattening, and 14.3% (2/14) had partial flattening. Both acute and late toxicities were mild, with only a single instance of grade 3 toxicity (dermatitis). CONCLUSION: Our study confirms that radiation therapy has a role in reducing the risk of keloid recurrence post-operatively, and plays an important role in the definitive management of unresectable keloids.

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.

Wound Healing: Cellular Review With Specific Attention to Postamputation Care.

Wound healing is crucial for survival, prevention of infection, and restoration of tissue function. The immune system drives this process with 3 main phases: inflammation, proliferation, and remodeling. Keloids and hypertrophic scars reveal disruptions in these phases, underscoring the balance needed for healing. Limb amputation, a life-changing event, demands careful consideration for healing and function. Factors such as amputation level, surgical technique, and prosthetic fitting shape outcomes, while complications such as heterotopic ossification challenge recovery. Treatment advances including statins and stem cell therapy hold promise, with dermatologists poised to contribute substantially to postamputation care.

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

BACKGROUND: Our study aims to delineate the miRSNP-microRNA-gene-pathway interactions in the context of hypertrophic scars (HS) and keloids. MATERIALS AND METHODS: 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. RESULTS: Our results revealed a total of 429 hub genes, with a strong enrichment in signaling pathways related to proteoglycans in cancer, focal adhesion, TGF-ß, 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. CONCLUSIONS: 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.