CYT997 Induces Apoptosis in Hypertrophic Scar Fibroblasts and Inhibits Scar Formation.

IF 4.2 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Xia Li, Fan Tian, Zhen-Yu Zhang, Jun-Jie Wu, Zheng-Dong Yuan, Feng-Lai Yuan, Jinghua Chen
{"title":"CYT997 Induces Apoptosis in Hypertrophic Scar Fibroblasts and Inhibits Scar Formation.","authors":"Xia Li, Fan Tian, Zhen-Yu Zhang, Jun-Jie Wu, Zheng-Dong Yuan, Feng-Lai Yuan, Jinghua Chen","doi":"10.1016/j.ejphar.2025.177815","DOIUrl":null,"url":null,"abstract":"<p><p>Emerging evidence indicates that hypertrophic scars (HS) display tumor-like behaviors, characterized by excessive, rapid cellular proliferation. To investigate potential therapeutic interventions, this study focused on the effects of CYT997, a novel anti-cancer drug, on hypertrophic scar fibroblasts (HSFs). HS tissues were collected from patients and compared with normal skin samples. CYT997 decreased HSF viability in a concentration-dependent manner, with a selected concentration for further experiments. It selectively induced apoptosis in HSFs but not in normal fibroblasts, as shown by flow cytometry and fluorescence microscopy. CYT997 also reduced HSF migration, contractility, and expression of collagen I and α-smooth muscle actin (α-SMA), indicating decreased fibrosis. In a rabbit ear hypertrophic scar model, CYT997 treatment inhibited scar formation, reduced the scar elevation index, and promoted apoptosis in HSFs. It also regulated apoptosis-related proteins poly(ADP-ribose) polymerase (PARP) and caspase-3 in HSFs. These findings suggest that CYT997 has potential as a targeted therapy for hypertrophic scars by inducing apoptosis in HSFs and reducing fibrotic activity.</p>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":" ","pages":"177815"},"PeriodicalIF":4.2000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ejphar.2025.177815","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Emerging evidence indicates that hypertrophic scars (HS) display tumor-like behaviors, characterized by excessive, rapid cellular proliferation. To investigate potential therapeutic interventions, this study focused on the effects of CYT997, a novel anti-cancer drug, on hypertrophic scar fibroblasts (HSFs). HS tissues were collected from patients and compared with normal skin samples. CYT997 decreased HSF viability in a concentration-dependent manner, with a selected concentration for further experiments. It selectively induced apoptosis in HSFs but not in normal fibroblasts, as shown by flow cytometry and fluorescence microscopy. CYT997 also reduced HSF migration, contractility, and expression of collagen I and α-smooth muscle actin (α-SMA), indicating decreased fibrosis. In a rabbit ear hypertrophic scar model, CYT997 treatment inhibited scar formation, reduced the scar elevation index, and promoted apoptosis in HSFs. It also regulated apoptosis-related proteins poly(ADP-ribose) polymerase (PARP) and caspase-3 in HSFs. These findings suggest that CYT997 has potential as a targeted therapy for hypertrophic scars by inducing apoptosis in HSFs and reducing fibrotic activity.

CYT997诱导增生性瘢痕成纤维细胞凋亡并抑制瘢痕形成
新出现的证据表明,增生性疤痕(HS)表现出肿瘤样行为,其特征是过度、快速的细胞增殖。为了探讨潜在的治疗干预措施,本研究重点研究了新型抗癌药物CYT997对增生性瘢痕成纤维细胞(hsf)的影响。收集患者的HS组织并与正常皮肤样本进行比较。CYT997以浓度依赖的方式降低HSF活力,并选择浓度进行进一步实验。流式细胞术和荧光显微镜显示,它选择性地诱导hsf细胞凋亡,而非正常成纤维细胞凋亡。CYT997还减少了HSF的迁移、收缩性以及I型胶原和α-平滑肌肌动蛋白(α-SMA)的表达,表明纤维化减少。在兔耳增生性瘢痕模型中,CYT997处理抑制瘢痕形成,降低瘢痕升高指数,促进hsf细胞凋亡。它还调节hsf中凋亡相关蛋白多聚(adp -核糖)聚合酶(PARP)和caspase-3。这些发现表明,CYT997有潜力通过诱导hsf细胞凋亡和降低纤维化活性作为增生性疤痕的靶向治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
9.00
自引率
0.00%
发文量
572
审稿时长
34 days
期刊介绍: The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信