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定义成熟和发育中的瘢痕疙瘩独特的基因表达谱。

Defining a Unique Gene Expression Profile in Mature and Developing Keloids.

作者信息

Zhu Yuan O, MacDonnell Scott, Kaplan Theodore, Liu Chien, Ali Yasmeen, Rangel Stephanie M, Wipperman Matthew F, Belback Madeleine, Sun Daphne S, Ren Ziyou, Zhou Xiaolong Alan, Halasz Gabor, Morton Lori, Kundu Roopal V

机构信息

Regeneron Pharmaceutical, Tarrytown, New York, USA.

Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

出版信息

JID Innov. 2023 May 19;3(5):100211. doi: 10.1016/j.xjidi.2023.100211. eCollection 2023 Sep.

DOI:10.1016/j.xjidi.2023.100211
PMID:37564104
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10410242/
Abstract

Keloids are benign, fibroproliferative dermal tumors that typically form owing to abnormal wound healing. The current standard of care is generally ineffective and does not prevent recurrence. To characterize keloid scars and better understand the mechanism of their formation, we performed transcriptomic profiling of keloid biopsies from a total of 25 subjects of diverse racial and ethnic origins, 15 of whom provided a paired nonlesional sample, a longitudinal sample, or both. The transcriptomic signature of nonlesional skin biopsies from subjects with keloids resembled that of control skin at baseline but shifted to closely match that of keloid skin after dermal trauma. Peripheral keloid skin and rebiopsied surrounding normal skin both showed upregulation of epithelial-mesenchymal transition markers, extracellular matrix organization, and collagen genes. These keloid signatures strongly overlapped those from healthy wound healing studies, usually with greater perturbations, reinforcing our understanding of keloids as dysregulated and exuberant wound healing. In addition, 219 genes uniquely regulated in keloids but not in normal injured or uninjured skin were also identified. This study provides insights into mature and developing keloid signatures that can act as a basis for further validation and target identification in the search for transformative keloid treatments.

摘要

瘢痕疙瘩是一种良性的纤维增生性皮肤肿瘤,通常由于伤口愈合异常而形成。目前的护理标准通常效果不佳,且无法预防复发。为了对瘢痕疙瘩进行特征描述并更好地理解其形成机制,我们对来自25名不同种族和族裔受试者的瘢痕疙瘩活检样本进行了转录组分析,其中15名受试者提供了配对的非病变样本、纵向样本或两者皆有。瘢痕疙瘩患者非病变皮肤活检样本的转录组特征在基线时与对照皮肤相似,但在皮肤创伤后转变为与瘢痕疙瘩皮肤紧密匹配。瘢痕疙瘩外周皮肤和再次活检的周围正常皮肤均显示上皮-间质转化标志物、细胞外基质组织和胶原蛋白基因上调。这些瘢痕疙瘩特征与健康伤口愈合研究中的特征高度重叠,通常干扰更大,这强化了我们对瘢痕疙瘩是失调且过度的伤口愈合的理解。此外,还鉴定出了219个在瘢痕疙瘩中独特调控但在正常受伤或未受伤皮肤中未调控的基因。这项研究为成熟和发展中的瘢痕疙瘩特征提供了见解,可作为进一步验证和靶点识别的基础,以寻找变革性的瘢痕疙瘩治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/581ad28ad6ab/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/aff7a023e95b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/44ad86aaf945/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/cdc39a7ca41c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/888609799f23/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/0bc50a066f40/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/a786375eba4d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/f5efb8306f8f/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/e53ff6a243b9/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/c9a339a7226e/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/a6d7872852f6/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/0837118fd1c5/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/581ad28ad6ab/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/aff7a023e95b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/44ad86aaf945/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/cdc39a7ca41c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/888609799f23/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/0bc50a066f40/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/a786375eba4d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/f5efb8306f8f/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/e53ff6a243b9/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/c9a339a7226e/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/a6d7872852f6/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/0837118fd1c5/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e791/10410242/581ad28ad6ab/gr12.jpg

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Exp Dermatol. 2022 Oct;31(10):1586-1596. doi: 10.1111/exd.14630. Epub 2022 Jul 3.
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AdRoit is an accurate and robust method to infer complex transcriptome composition.AdRoit 是一种推断复杂转录组组成的准确而稳健的方法。
Commun Biol. 2021 Oct 22;4(1):1218. doi: 10.1038/s42003-021-02739-1.
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Fibroblasts: Heterogeneous Cells With Potential in Regenerative Therapy for Scarless Wound Healing.
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Front Cell Dev Biol. 2021 Jul 20;9:713605. doi: 10.3389/fcell.2021.713605. eCollection 2021.
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Single-Cell RNA-Sequencing Reveals Lineage-Specific Regulatory Changes of Fibroblasts and Vascular Endothelial Cells in Keloids.单细胞RNA测序揭示瘢痕疙瘩中成纤维细胞和血管内皮细胞的谱系特异性调控变化。
J Invest Dermatol. 2022 Jan;142(1):124-135.e11. doi: 10.1016/j.jid.2021.06.010. Epub 2021 Jul 7.
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Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases.单细胞 RNA 测序揭示人类纤维化皮肤疾病中成纤维细胞的异质性和间充质成纤维细胞的增加。
Nat Commun. 2021 Jun 17;12(1):3709. doi: 10.1038/s41467-021-24110-y.
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