全面模块化分析疤痕亚型揭示潜在的分子机制和治疗靶点。
Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets.
发表日期:2023 Sep 11
作者:
Liang Liu, Lantian Lu, Min Qiu, Ning Han, Shijie Dai, Shuiping Shi, Shanshan He, Jing Zhang, Qingfeng Yan, Shuqing Chen
来源:
Genes & Diseases
摘要:
由创伤和伤口引起的病理性瘢痕,如肥厚性瘢痕和瘢痕痿痹,对外观、功能和心理造成了重大挑战。本研究对这些疾病进行了全面的转录组分析,旨在阐明潜在的分子机制和潜在的治疗靶点。我们采用了共表达和模块分析工具,鉴定出与不同病理生理过程和机制相关的重要基因簇,尤其是脂质代谢、皮脂产生、细胞能量代谢和皮肤屏障功能等。这项研究揭示了多种皮肤疾病的关键见解,包括毛囊炎、皮肤纤维化、纤维肉瘤和先天性鱼鳞病。特别关注了模块簇(MCluster)3,其中包括BLK、TRPV1和GABRD等高表达基因,可能对免疫调节具有潜在意义。初步的免疫组织化学验证支持了这些发现,显示了这些基因在免疫活性丰富的非纤维化样本中的高表达。此外,还探讨了瘢痕形成中不同细胞类型(如成纤维细胞、肌成纤维细胞、角质形成细胞和肥大细胞)的复杂相互作用,揭示了有希望的治疗策略。本研究强调了面向病理性瘢痕的靶向基因治疗的前景,为更个性化的治疗方法铺平了道路。结果需要进一步研究,以充分确定这些所鉴定的基因和途径在皮肤疾病发病机制和潜在治疗方面的作用。尽管如此,我们的工作为患有病理性瘢痕的患者铺就了个性化医学的坚实基础。© 2023 应用医学咨询有限公司和约翰威立公司发表的《国际创伤杂志》。
Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co-expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non-fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.