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单细胞RNA测序揭示皮肤瘢痕的细胞和基因异质性,以验证祛疤膏抑制增生性瘢痕的治疗效果及作用机制。

Single-Cell RNA-Sequencing Reveals the Cellular and Genetic Heterogeneity of Skin Scar to Verify the Therapeutic Effects and Mechanism of Action of Dispel-Scar Ointment in Hypertrophic Scar Inhibition.

作者信息

Li Zhaoyi, Yin Libo, Li Yuanyuan, Cao Yi, Zeng Haifeng

机构信息

The First Clinical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, China.

出版信息

Evid Based Complement Alternat Med. 2022 Jun 8;2022:7331164. doi: 10.1155/2022/7331164. eCollection 2022.

DOI:10.1155/2022/7331164
PMID:35722137
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9200508/
Abstract

Hypertrophic scarring (HS), caused by excessive fibrosis of injured skin, imposes a psychological burden and creates a source of distress that impairs the quality of life of affected individuals. However, the gold standard for HS treatment has not yet been determined due to the complicated and difficult nature of the routines and procedures involved. Previous studies have indicated that the topical application of certain active components found in traditional Chinese medicines shows potential as a therapeutic alternative for scars. Here, single-cell RNA-sequencing was performed to determine cellular heterogeneity and identify marker genes and mechanisms associated with HS. It was found that fibroblasts comprise the largest proportion of HS cell types. The marker genes that were highly expressed in fibroblasts were extracellular matrix (ECM)-related, whereas ECM-receptor interactions and the transforming growth factor (TGF)- signalling pathway were also found to be active. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, which was applied to identify the molecular compounds of Dispel-Scar Ointment (DSO), revealed 74 effective chemical components belonging to 14 types of constituents, such as flavonoids, tanshinones, salvianolic acids, glycosides, and phthalides. Furthermore, studies using rat scar models showed that the topical application of , , peach kernel, safflower, and motherwort exerted beneficial effects on fibroblasts. DSO promoted scar maturation and reduced scar areas, its efficacy being similar to that of topically applied silicone. Functional studies using immunofluorescence staining, western blotting, and quantitative real-time polymerase chain reaction demonstrated that DSO may target the TGF-/Smad pathway to inhibit collagen synthesis and promote ECM remodelling. However, further mechanistic research and single-drug prescription studies may be required to identify the specific effective compound or active ingredient of DSO, which would provide more substantial evidence regarding the potential therapeutic value of traditional herbs in HS.

摘要

肥厚性瘢痕(HS)由受损皮肤的过度纤维化引起,会给患者带来心理负担,并造成痛苦,影响患者的生活质量。然而,由于相关常规治疗和程序复杂困难,HS治疗的金标准尚未确定。先前的研究表明,中药中某些活性成分的局部应用显示出作为瘢痕治疗替代方法的潜力。在此,进行单细胞RNA测序以确定细胞异质性,并鉴定与HS相关的标记基因和机制。研究发现,成纤维细胞在HS细胞类型中占比最大。在成纤维细胞中高表达的标记基因与细胞外基质(ECM)相关,同时还发现ECM-受体相互作用和转化生长因子(TGF)信号通路也处于活跃状态。应用超高效液相色谱-四极杆飞行时间质谱法鉴定祛疤膏(DSO)的分子化合物,结果显示有74种有效化学成分,分属于14类成分,如黄酮类、丹参酮类、丹酚酸类、糖苷类和苯酞类。此外,使用大鼠瘢痕模型的研究表明,地榆、槐花、桃仁、红花和益母草的局部应用对成纤维细胞有有益作用。DSO促进瘢痕成熟并减小瘢痕面积,其疗效与局部应用硅胶相似。使用免疫荧光染色、蛋白质印迹和定量实时聚合酶链反应进行的功能研究表明,DSO可能靶向TGF-β/Smad通路以抑制胶原蛋白合成并促进ECM重塑。然而,可能需要进一步的机制研究和单药处方研究来确定DSO的具体有效化合物或活性成分,这将为传统草药在HS中的潜在治疗价值提供更确凿的证据。

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Distinct Regulatory Programs Control the Latent Regenerative Potential of Dermal Fibroblasts during Wound Healing.不同的调控程序控制皮肤成纤维细胞在伤口愈合过程中的潜伏再生潜能。
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