An updated review of the immunological mechanisms of keloid scars

Lee, Chih-Chun; Tsai, Chun‐Yi; Chen, Chih‐Hao; Yeh, Yuan-Chieh; Chung, Wen‐Hung; Chen, Chun‐Bing

doi:10.3389/fimmu.2023.1117630

Cited by 16 publications

(4 citation statements)

References 245 publications

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“…Overproduction of ECM is closely related to prolonged inflammation in keloid pathogenesis. Keloid formation is driven by multiple cytokines, growth factors, and transcription factors [ 2 , 35 ]. The study by Nangole et al [ 36 ] revealed that the high expression of proinflammatory cytokines in keloid impacts the sensitivity and increases the production of collagen on keloid fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Profibrotic Inflammatory Cytokines and Growth Factors Are Predicted as the Key Targets of Uncaria gambir (Hunter) Roxb. in Keloids: An Epistatic and Molecular Simulation Approach

Ningsih,

Fadilah,

Jusman

et al. 2024

Pharmaceuticals

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Keloid is characterized as the fibrotic tissue resulting from the increase of fibroblast activity. Uncaria gambir (Hunter) Roxb. possesses bioactive compounds that have potential as antifibrotic agents, while the mechanism of action in keloid has not yet been elucidated. The aim of this study was to investigate the interaction of gambir bioactive compounds with keloid target proteins using an epistatic and molecular simulation approach. The known bioactive compounds of gambir targets and keloid-related protein targets were screened using databases. The network was constructed and analyzed to obtain the core protein targets. The targets were enriched to describe the Gene Ontology (GO) and pathway related to the proteins. Eleven targets were defined as the main targets of gambir bioactive compounds related to keloid disease. Gambiriin C, Isogambirine, and Procyanidin B1 were identified as the most promising compounds with the highest binding energy to transforming growth factor beta 1 (TGFβ1), AKT serine/threonine kinase 1 (AKT1), and matrix metallopeptidase 1 (MMP1) as the target proteins. GO enrichment and pathway analysis found that gambir bioactive compounds may act on keloid-related target proteins to regulate cell proliferation, migration, transcription, and signal transduction activity via profibrotic cytokine and growth factor signaling pathways. This study provides a reference for potential targets, compounds, and pathways to explain the mechanism of gambir against keloid.

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Section: Discussionmentioning

confidence: 99%

Profibrotic Inflammatory Cytokines and Growth Factors Are Predicted as the Key Targets of Uncaria gambir (Hunter) Roxb. in Keloids: An Epistatic and Molecular Simulation Approach

Ningsih,

Fadilah,

Jusman

et al. 2024

Pharmaceuticals

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“…Keloid development involves a local infiltration of inflammatory cells including mast cells [7]. Cocultured HMC-1 stimulated the collagen 1 expression of KFs, and it was attenuated by a blockade of PI3K, mTOR, and p38 MAPK [107].…”

Section: The Potential Of Natural Product-based Therapy and Future Tasksmentioning

confidence: 99%

“…Keloid is a type of scarring that occurs due to abnormally high cell proliferation and the excessive accumulation of ECM during the healing process of a skin injury [7,8]. Keloids are similar to hypertrophic scars in that they involve the proliferation of dermal fibroblasts and accumulation of ECM, but keloids differ in that they grow beyond the boundaries of the initial injury [9].…”

Section: Introductionmentioning

confidence: 99%

Insights into How Plant-Derived Extracts and Compounds Can Help in the Prevention and Treatment of Keloid Disease: Established and Emerging Therapeutic Targets

Boo

2024

IJMS

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Keloid is a disease in which fibroblasts abnormally proliferate and synthesize excessive amounts of extracellular matrix, including collagen and fibronectin, during the healing process of skin wounds, causing larger scars that exceed the boundaries of the original wound. Currently, surgical excision, cryotherapy, radiation, laser treatment, photodynamic therapy, pressure therapy, silicone gel sheeting, and pharmacotherapy are used alone or in combinations to treat this disease, but the outcomes are usually unsatisfactory. The purpose of this review is to examine whether natural products can help treat keloid disease. I introduce well-established therapeutic targets for this disease and various other emerging therapeutic targets that have been proposed based on the phenotypic difference between keloid-derived fibroblasts (KFs) and normal epidermal fibroblasts (NFs). We then present recent studies on the biological effects of various plant-derived extracts and compounds on KFs and NFs. Associated ex vivo, in vivo, and clinical studies are also presented. Finally, we discuss the mechanisms of action of the plant-derived extracts and compounds, the pros and cons, and the future tasks for natural product-based therapy for keloid disease, as compared with existing other therapies. Extracts of Astragalus membranaceus, Salvia miltiorrhiza, Aneilema keisak, Galla Chinensis, Lycium chinense, Physalis angulate, Allium sepa, and Camellia sinensis appear to modulate cell proliferation, migration, and/or extracellular matrix (ECM) production in KFs, supporting their therapeutic potential. Various phenolic compounds, terpenoids, alkaloids, and other plant-derived compounds could modulate different cell signaling pathways associated with the pathogenesis of keloids. For now, many studies are limited to in vitro experiments; additional research and development are needed to proceed to clinical trials. Many emerging therapeutic targets could accelerate the discovery of plant-derived substances for the prevention and treatment of keloid disease. I hope that this review will bridge past, present, and future research on this subject and provide insight into new therapeutic targets and pharmaceuticals, aiming for effective keloid treatment.

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“…It has been demonstrated that exosomes isolated from human adipose MSCs can reduce the proliferation of scar fibroblasts and collagen synthesis by inhibiting the TGF-β/Smad signaling pathway and improve scar formation in burn wounds [49]. Keloid fibroblasts are a specific type of fibroblasts that appear during the wound healing process; they are highly proliferative and secretory but lack the ability to degrade and remodel the extracellular matrix, leading to the excessive deposition of extracellular matrix and fibrosis of the tissue [50]. The TGF-β/Smad signaling pathway is a signal transduction pathway involved in cell proliferation and differentiation, and plays an important role in the regulation of scar formation [51].…”

Section: The Wound Healing-promoting Mechanisms Of Mesenchymal Stem C...mentioning

confidence: 99%

The Role and Prospects of Mesenchymal Stem Cells in Skin Repair and Regeneration

Wu,

Sun,

et al. 2024

Biomedicines

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Mesenchymal stem cells (MSCs) have been recognized as a cell therapy with the potential to promote skin healing. MSCs, with their multipotent differentiation ability, can generate various cells related to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. In addition, MSCs promote neovascularization, cellular regeneration, and tissue healing through mechanisms including paracrine and autocrine signaling. Due to these characteristics, MSCs have been extensively studied in the context of burn healing and chronic wound repair. Furthermore, during the investigation of MSCs, their unique roles in skin aging and scarless healing have also been discovered. In this review, we summarize the mechanisms by which MSCs promote wound healing and discuss the recent findings from preclinical and clinical studies. We also explore strategies to enhance the therapeutic effects of MSCs. Moreover, we discuss the emerging trend of combining MSCs with tissue engineering techniques, leveraging the advantages of MSCs and tissue engineering materials, such as biodegradable scaffolds and hydrogels, to enhance the skin repair capacity of MSCs. Additionally, we highlight the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies as a future direction in stem cell-based treatments, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.

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An updated review of the immunological mechanisms of keloid scars

Cited by 16 publications

References 245 publications

Profibrotic Inflammatory Cytokines and Growth Factors Are Predicted as the Key Targets of Uncaria gambir (Hunter) Roxb. in Keloids: An Epistatic and Molecular Simulation Approach

Profibrotic Inflammatory Cytokines and Growth Factors Are Predicted as the Key Targets of Uncaria gambir (Hunter) Roxb. in Keloids: An Epistatic and Molecular Simulation Approach

Insights into How Plant-Derived Extracts and Compounds Can Help in the Prevention and Treatment of Keloid Disease: Established and Emerging Therapeutic Targets

The Role and Prospects of Mesenchymal Stem Cells in Skin Repair and Regeneration

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