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

增生性瘢痕 瘢痕疙瘩 SMAD公司 细胞外基质 核糖核酸 细胞 伤口愈合 纤维化 疤痕 生物 细胞生物学 癌症研究 化学 信号转导 生物化学 基因 医学 病理 遗传学 解剖
作者
Zhaoyi Li,Libo Yin,Yuanyuan Li,Yi Cao,Haifeng Zeng
出处
期刊:Evidence-based Complementary and Alternative Medicine [Hindawi Publishing Corporation]
卷期号:2022: 1-27 被引量:2
标识
DOI:10.1155/2022/7331164
摘要

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)-β 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, in vivo studies using rat scar models showed that the topical application of Salvia miltiorrhiza, Ligusticum chuanxiong, 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-β/Smad pathway to inhibit collagen synthesis and promote ECM remodelling. However, further in vitro 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.
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