Burns & Trauma最新文献

{"title":"Type 3 deiodinase activation mediated by the Shh/Gli1 axis promotes sepsis-induced metabolic dysregulation in skeletal muscles","authors":"Gang Wang, Tao Gao, Yijiang Liu, Jianfeng Duan, Huimin Lu, Anqi Jiang, Yun Xu, Xiaolan Lu, Xiaoyao Li, Yong Wang, Wenkui Yu","doi":"10.1093/burnst/tkae066","DOIUrl":"https://doi.org/10.1093/burnst/tkae066","url":null,"abstract":"Background Non-thyroidal illness syndrome is commonly observed in critically ill patients, characterized by the inactivation of systemic thyroid hormones (TH), which aggravates metabolic dysfunction. Recent evidence indicates that enhanced TH inactivation is mediated by the reactivation of type 3 deiodinase (Dio3) at the tissue level, culminating in a perturbed local metabolic equilibrium. This study assessed whether targeted inhibition of Dio3 can maintain tissue metabolic homeostasis under septic conditions and explored the mechanism behind Dio3 reactivation. Methods A retrospective clinical study was conducted to investigate the attributes of rT3. The expression of Dio3 was detected by immunoblotting, immunofluorescence, and immunohistochemical staining in tissues extracted from CLP-induced septic rats and human biopsy samples. In addition, the effect of Dio3 inhibition on skeletal muscle metabolism was observed in rats with targeted Dio3 knockdown using an adeno-associated virus. The effectiveness of Sonic hedgehog (Shh) signaling inhibition on systemic TH levels was observed in CLP-induced septic rats receiving cyclopamine. The mechanisms underlying such inhibition were explored using immunoblotting, RNA-seq, and chromatin immunoprecipitation–qPCR assays. Results The main product of Dio3, rT3, is strongly associated with organ function. Early sepsis leads to significant upregulation of Dio3 in the skeletal muscles and lung tissues of septic rats. The targeted inhibition of Dio3 in skeletal muscle restores TH responsiveness, prevents fast-to-slow fiber conversion, preserves glucose transporter type 4 functionality, and maintains metabolic balance between protein synthesis and proteolysis, which leads to preserved muscle mass. The reactivation of Dio3 is transcriptionally regulated by the Shh pathway induced by the signal transducer and activator of transcription 3. Conclusions The suppression of Dio3 restores tissue TH actions, attenuates proteolysis, and ameliorates anabolic resistance in the skeletal muscles of septic rats, thereby improving local metabolic homeostasis. Our results provide insights into the mechanisms of Dio3 reactivation and its critical role in local metabolic alterations induced by sepsis, while also suggesting novel targets aimed at ameliorating tissue-specific metabolic disorders.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"20 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asiaticoside-nitric oxide synergistically accelerate diabetic wound healing by regulating key metabolites and SRC/STAT3 signaling","authors":"Xingrui Mu, Jitao Chen, Huan Zhu, Junyu Deng, Xingqian Wu, Wenjie He, Penghui Ye, Rifang Gu, Youzhi Wu, Felicity Han, Xuqiang Nie","doi":"10.1093/burnst/tkaf009","DOIUrl":"https://doi.org/10.1093/burnst/tkaf009","url":null,"abstract":"Background Diabetic wounds pose significant clinical challenges due to impaired healing processes, often resulting in chronic, non-healing ulcers. Asiaticoside (AC), a natural triterpene derivative from Centella asiatica, has demonstrated notable anti-inflammatory and wound-healing properties. However, the synergistic effects of nitric oxide (NO)—a recognized promoter of wound healing—combined with AC in treating diabetic wounds remain inadequately explored. Methods Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was utilized to identify differential metabolites and dysregulated metabolic pathways associated with diabetic wounds. Molecular docking analyses were conducted to confirm the binding affinity of AC to key therapeutic targets. The effects of Asiaticoside-nitric oxide hydrogel (ACNO) on gene and protein expression were evaluated using RT-qPCR and western blotting. In vitro experiments using SRC agonists and inhibitors were performed to investigate the impact of ACNO therapy on the expression of SRC, STAT3, and other proteins in HaCaT cells. Results Metabolomic profiling revealed that diabetic wounds in mice exhibited marked metabolic dysregulation, which was attenuated by ACNO treatment. Key metabolites modulated by ACNO included mandelic acid, lactic acid, and 3-hydroxyisovaleric acid. The primary metabolic pathways involved were methyl histidine metabolism and the malate–aspartate shuttle. Immunofluorescence staining confirmed that ACNO therapy enhanced angiogenesis, promoted cellular proliferation, and facilitated diabetic wound closure. RT–qPCR data demonstrated that ACNO regulated the transcription of critical genes (SRC, STAT3, EGFR, and VEGFA). Notably, ACNO attenuated SRC/STAT3 pathway activation while concurrently upregulating EGFR and VEGFA expression. Conclusions These findings emphasize the therapeutic potential of ACNO hydrogel in diabetic wound healing through the modulation of metabolic pathways and the SRC/STAT3 signaling axis. By correlating altered metabolites with molecular targets, this study elucidates the pharmacodynamic foundation for ACNO’s pre-clinical application and provides valuable insights into the development of targeted therapies for diabetic wound management.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"2 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in the role of neuroregulation in skin wound healing","authors":"Abdullah Al Mamun, Chuxiao Shao, Peiwu Geng, Shuanghu Wang, Jian Xiao","doi":"10.1093/burnst/tkae072","DOIUrl":"https://doi.org/10.1093/burnst/tkae072","url":null,"abstract":"Neuroregulation during skin wound healing involves complex interactions between the nervous system and intricate tissue repair processes. The skin, the largest organ, depends on a complex system of nerves to manage responses to injury. Recent research has emphasized the crucial role of neuroregulation in maximizing wound healing outcomes. Recently, researchers have also explained the interactive contact between the peripheral nervous system and skin cells during the different phases of wound healing. Neurotransmitters and neuropeptides, once observed as simple signalling molecules, have since been recognized as effective regulators of inflammation, angiogenesis, and cell proliferation. The significance of skin innervation and neuromodulators is underscored by the delayed wound healing observed in patients with diabetes and the regenerative capabilities of foetal skin. Foetal skin regeneration is influenced by the neuroregulatory environment, immature immune system, abundant growth factors, and increased pluripotency of cells. Foetal skin cells exhibit greater flexibility and specialized cell types, and the extracellular matrix composition promotes regeneration. The extracellular matrix composition of foetal skin promotes regeneration, making it more capable than adult skin because neuroregulatory signals affect skin regeneration. The understanding of these systems can facilitate the development of therapeutic strategies to alter the nerve supply to the skin to enhance the process of wound healing. Neuroregulation is being explored as a potential therapeutic strategy for enhancing skin wound repair. Bioelectronic strategies and neuromodulation techniques can manipulate neural signalling, optimize the neuroimmune axis, and modulate inflammation. This review describes the function of skin innervation in wound healing, emphasizing the importance of neuropeptides released by sensory and autonomic nerve fibres. This article discusses significant discoveries related to neuroregulation and its impact on skin wound healing.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"39 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing diabetic muscle repair through W-GA nanodots: a nanomedicinal approach to ameliorate myopathy in type 2 diabetes","authors":"Shan Liu, Renwen Wan, QingRong Li, Yisheng Chen, Yanwei He, Xingting Feng, Patrick Shu-Hang Yung, Zhiwen Luo, Xianwen Wang, Chen Chen","doi":"10.1093/burnst/tkae059","DOIUrl":"https://doi.org/10.1093/burnst/tkae059","url":null,"abstract":"Objective Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly impairs muscle regeneration following injuries, contributing to numerous complications and reduced quality of life. There is an urgent need for therapeutic strategies that can enhance muscle regeneration and alleviate these pathological mechanisms. In this study, we evaluate the therapeutic efficacy of W-GA nanodots, which are composed of gallic acid (GA) and tungstate (W6+), on muscle regeneration in type 2 diabetes mellitus (T2D)-induced muscle injury, with a focus on their anti-inflammatory and antioxidative effects. Methods This study synthesized ultrasmall W-GA nanodots that were optimized for improved stability and bioactivity under physiological conditions. In vitro assessments included cell viability, apoptosis, reactive oxygen species (ROS) generation, and myotube differentiation in C2C12 myoblasts under hyperglycemic conditions. In vivo, T2D was induced in C57BL/6 mice, followed by muscle injury and treatment with W-GA. Muscle repair, fibrosis, and functional recovery were assessed through histological analysis and gait analysis using the CatWalk system. Results The W-GA nanodots significantly enhanced muscle cell proliferation, decreased ROS, and reduced apoptosis in vitro. In vivo, compared with the control group, the W-GA-treated group exhibited notably improved muscle regeneration, decreased fibrosis, and enhanced functional recovery. The treatment notably modulated the inflammatory response and oxidative stress in diabetic muscle tissues, facilitating improved regenerative dynamics and muscle function. Conclusions W-GA nanodots effectively counter the pathological mechanisms of diabetic myopathy by enhancing regenerative capacity and reducing oxidative stress and inflammation. This nanomedicine approach offers a promising therapeutic avenue for improving muscle health and overall quality of life in individuals suffering from T2D. However, further studies are needed to explore the clinical applications and long-term efficacy of these nanodots in preventing diabetic complications.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"61 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional metal–organic frameworks as promising nanomaterials for antimicrobial strategies","authors":"Qian-Jin Li, Fei Xing, Wen-Ting Wu, Man Zhe, Wen-Qian Zhang, Lu Qin, Li-Ping Huang, Long-Mei Zhao, Rui Wang, Ming-Hui Fan, Chen-Yu Zou, Wei-Qiang Duan, Jesse Li-Ling, Hui-Qi Xie","doi":"10.1093/burnst/tkaf008","DOIUrl":"https://doi.org/10.1093/burnst/tkaf008","url":null,"abstract":"Bacterial infections pose a serious threat to human health. While antibiotics have been effective in treating bacterial infectious diseases, antibiotic resistance significantly reduces their effectiveness. Therefore, it is crucial to develop new and effective antimicrobial strategies. Metal–organic frameworks (MOFs) have become ideal nanomaterials for various antimicrobial applications due to their crystalline porous structure, tunable size, good mechanical stability, large surface area, and chemical stability. Importantly, the performance of MOFs can be adjusted by changing the synthesis steps and conditions. Pure MOFs can release metal ions to modulate cellular behaviors and kill various microorganisms. Additionally, MOFs can act as carriers for delivering antimicrobial agents in a desired manner. Importantly, the performance of MOFs can be adjusted by changing the synthesis steps and conditions. Furthermore, certain types of MOFs can be combined with traditional photothermal or other physical stimuli to achieve broad-spectrum antimicrobial activity. Recently an increasing number of researchers have conducted many studies on applying various MOFs for diseases caused by bacterial infections. Based on this, we perform this study to report the current status of MOFs-based antimicrobial strategy. In addition, we also discussed some challenges that MOFs currently face in biomedical applications, such as biocompatibility and controlled release capabilities. Although these challenges currently limit their widespread use, we believe that with further research and development, new MOFs with higher biocompatibility and targeting capabilities can provide diversified treatment strategies for various diseases caused by bacterial infections.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"33 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles in burn injury: roles, mechanisms, and applications","authors":"Min Wang, Xinyu Zhao, Yuyu Cui, Hengshuo Gui, Shuai Wang, Zhuang Liu, Xianwen Wang","doi":"10.1093/burnst/tkaf006","DOIUrl":"https://doi.org/10.1093/burnst/tkaf006","url":null,"abstract":"Burn injuries are associated with high morbidity and mortality, and severe burns trigger many pathophysiological reactions, such as metabolic changes, distributive shock, and inflammatory responses, which are potentially devastating to patients. Burn wound management necessitates infection prevention, anti-inflammation, pain management, and growth factor management, but significant obstacles remain. Extracellular vesicles (EVs) are lipid bilayer vesicles secreted by various cell types, including mammalian cells, plant cells, and even prokaryotes, They are widely involved in various biological processes, such as cell survival, neovascularization, and immunomodulation. EVs are abundant in components that can play a significant role in different stages of wound repair and at different subcellular levels simultaneously by transporting various active contents, such as proteins and nucleic acids. Moreover, EVs are detectable in many biofluids of burn injury patients and are thus regarded as novel biomarkers for monitoring therapeutic response and predicting prognosis. This review summarizes the biological roles of EVs and their mechanisms of action in burn injury are summarized. The prospects and opportunities for the clinical application of EVs in burn wounds are also discussed. This review will stimulate and guide additional in-depth studies of EVs in burn wound repair, provide a new therapy for burn wounds, and provide a reference and guidance for applying EVs in clinical wound repair.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"25 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise therapy facilitates neural remodeling and functional recovery post-spinal cord injury via PKA/CREB signaling pathway modulation in rats","authors":"Xinwang Ying, Qingfeng Xie, Yanfang Zhao, Jiamen Shen, Junqing Huang, Zhiyi Feng, Liuxi Chu, Junpeng Xu, Dawei Jiang, Ping Wu, Yanming Zuo, Shengcun Li, Chang Jiang, Xiaokun Li, Zhouguang Wang","doi":"10.1093/burnst/tkae058","DOIUrl":"https://doi.org/10.1093/burnst/tkae058","url":null,"abstract":"Background Neuronal structure is disrupted after spinal cord injury (SCI), causing functional impairment. The effectiveness of exercise therapy (ET) in clinical settings for nerve remodeling post-SCI and its underlying mechanisms remain unclear. This study aims to explore the effects and related mechanisms of ET on nerve remodeling in SCI rats. Methods We randomly assigned rats to various groups: sham-operated group, sham-operated + ET, SCI alone, SCI + H89, SCI + ET, and SCI + ET + H89. Techniques including motor-evoked potential (MEP), video capture and analysis, the Basso–Beattie–Bresnahan (BBB) scale, western blotting, transmission electron microscopy, hematoxylin and eosin staining, Nissl staining, glycine silver staining, immunofluorescence, and Golgi staining were utilized to assess signal conduction capabilities, neurological deficits, hindlimb performance, protein expression levels, neuron ultrastructure, and tissue morphology. H89—an inhibitor that targets the protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway—was employed to investigate molecular mechanisms. Results This study found that ET can reduce neuronal damage in rats with SCI, protect residual tissue, promote the remodeling of motor neurons, neurofilaments, dendrites/axons, synapses, and myelin sheaths, reorganize neural circuits, and promote motor function recovery. In terms of mechanism, ET mainly works by mediating the PKA/CREB signaling pathway in neurons. Conclusions Our findings indicated that: (1) ET counteracted the H89-induced suppression of the PKA/CREB signaling pathway following SCI; (2) ET significantly alleviated neuronal injury and improved motor dysfunction; (3) ET facilitated neuronal regeneration by mediating the PKA/CREB signaling pathway; (4) ET enhanced synaptic and dendritic spine plasticity, as well as myelin sheath remodeling, post-SCI through the PKA/CREB signaling pathway.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"75 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the dual roles of apoptosis and necroptosis in diabetic wound healing: implications for therapeutic intervention","authors":"Xingqian Wu, Rifang Gu, Ming Tang, Xingrui Mu, Wenjie He, Xuqiang Nie","doi":"10.1093/burnst/tkae061","DOIUrl":"https://doi.org/10.1093/burnst/tkae061","url":null,"abstract":"Wound healing is a complex and multistep biological process that involves the cooperation of various cell types. Programmed cell death, including apoptosis and necrotizing apoptosis, plays a crucial role in this process. Apoptosis, a controlled and orderly programmed cell death regulated by genes, helps eliminate unnecessary or abnormal cells and maintain internal environmental stability. It also regulates various cell functions and contributes to the development of many diseases. In wound healing, programmed cell death is essential for removing inflammatory cells and forming scars. On the other hand, necroptosis, another form of programmed cell death, has not been thoroughly investigated regarding its role in wound healing. This review explores the changes and apoptosis of specific cell groups during wound healing after an injury and delves into the potential underlying mechanisms. Furthermore, it briefly discusses the possible mechanisms linking wound inflammation and fibrosis to apoptosis in wound healing. By understanding the relationship between apoptosis and wound healing and investigating the molecular mechanisms involved in apoptosis regulation, new strategies for the clinical treatment of wound healing may be discovered.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"52 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics perspective: mechanisms of gastrointestinal injury repair","authors":"Haibin Zhao, Zhigang Zhang, Hongyu Liu, Mingxiu Ma, Peng Sun, Yang Zhao, Xun Liu","doi":"10.1093/burnst/tkae057","DOIUrl":"https://doi.org/10.1093/burnst/tkae057","url":null,"abstract":"In this review, we examine the significance of multi-omics technologies in understanding the plethora of intricate processes that activate gastrointestinal (GI) injury repair. Multi-omics, which includes genomics, transcriptomics, proteomics, and metabolomics, allows intricate mapping of cellular responses and molecular pathways involved in GI repair. We highlight the potential of multi-omics to discover previously unknown therapeutic targets or elucidate the molecular basis of the pathogenesis of GI. Furthermore, we explore the possibilities of integrating omics data to improve prediction models, and summarize the state-of-the-art technological developments and persisting obstacles that hinder the translation of multi-omics into clinical practice. Finally, innovative multi-omics approaches that can improve patient outcomes and advance therapeutic strategies in GI medicine are discussed.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"105 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor activity-modifying protein 1 regulates the differentiation of mouse skin fibroblasts by downregulating α-SMA expression via suppression of high mobility group AT-hook 1 to promote skin wound repair","authors":"Ru Song, Jiaxu Ma, Siyuan Yin, Zhenjie Wu, Chunyan Liu, Rui Sun, Guoqi Cao, Yongpan Lu, Jian Liu, Linqi Su, Yibing Wang","doi":"10.1093/burnst/tkae068","DOIUrl":"https://doi.org/10.1093/burnst/tkae068","url":null,"abstract":"Background Skin innervation is very important for normal wound healing, and receptor activity-modifying protein 1 (RAMP1) has been reported to modulate calcitonin gene-related peptide (CGRP) receptor function and thus be a potential treatment target. This study aimed to elucidate the intricate regulatory effect of RAMP1 on skin fibroblast function, thereby addressing the existing knowledge gap in this area. Methods Immunohistochemical staining and immunofluorescence (IF) staining were used to measure the dynamic changes in the expression of RAMP1 and α-smooth muscle actin (α-SMA) in skin wound tissue in mice. Mouse skin fibroblasts (MSFs) stably transfected with Tet-on-Flag-RAMP1 overexpression (OE) and Tet-on-Flag control (Ctrl) lentiviruses were constructed for in vitro experiments. High mobility group AT-hook 1 (HMGA1) plasmids and α-SMA plasmids were used to overexpress HMGA1 and α-SMA, respectively. An α-SMA siRNA was used to silence α-SMA. Quantitative real-time polymerase chain reaction (qPCR), western blot and IF staining analyses were used to determine the mRNA and protein levels in the cells in different groups. A scratch wound healing assay was used to evaluate the cell migration ability of different groups. Cleavage under targets and release using nuclease (CUT & RUN) assays and dual-luciferase reporter assays were used to predict and verify the interaction between HMGA1 and the α-SMA promoter. Results RAMP1 and α-SMA protein expression levels in the dermis changed dynamically and were negatively correlated during dorsal skin wound healing in mice. RAMP1 OE in vitro inhibited the differentiation and promoted the migration of MSFs by decreasing α-SMA expression via the suppression of HMGA1, which was shown for the first time to bind to the α-SMA promoter and increase α-SMA transcription. RAMP1 OE also modulated extracellular matrix (ECM) synthesis and remodeling by promoting collagen III and MMP9 expression and decreasing collagen I, MMP2, and tissue inhibitor of metalloproteinases 1 expression. Conclusions Our findings suggest that RAMP1 OE decreases differentiation and promotes migration in MSFs by downregulating α-SMA expression via the suppression of HMGA1 and modulates ECM synthesis and remodeling, revealing a novel mechanism regulating α-SMA transcription, providing new insights into the RAMP1-mediated regulation of fibroblast function, and identifying effective nerve-related targets for skin wound repair.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"137 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}