Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development
- Burns & Trauma Vol. 10, Issue 1, (2022)
- 作者机构：
1. Department of Dermatology
2. Southern Medical University
3. Molecular Diagnosis and Treatment Center for Infectious Diseases
4. Department of Dermatologic Surgery
- 作者简介：
- 基金信息：
DOI：10.1093/burnst/tkac013
CLC：Published：2022，
Published Online：9 May 2022，
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Qi Wang, Yixiu Zhong, Zhijia Li, Dingheng Zhu, Hongyan Lu, Pingjiao Chen, Changxing Li, Xuebiao Peng, Qian Li, Kang Zeng, Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development, Burns & Trauma, Volume 10, 2022, tkac013, https://doi.org/10.1093/burnst/tkac013
Qi Wang, Yixiu Zhong, Zhijia Li, Dingheng Zhu, Hongyan Lu, Pingjiao Chen, Changxing Li, Xuebiao Peng, Qian Li, Kang Zeng, Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development, Burns & Trauma, Volume 10, 2022, tkac013, https://doi.org/10.1093/burnst/tkac013 DOI：
摘要
Abstract
BackgroundA keloid is a disease of excessive fibrosis that is characterized by the aberrant proliferation of fibroblasts. However
the molecular mechanisms of fibroblasts during the development of keloids remain unclear. This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts
providing new ideas for the prevention and treatment of keloids.MethodsWe utilized bioinformatics tools to analyze data from keloid fibroblasts (KFs) available in the Gene Expression Omnibus (GEO) database to identify the key genes involved in keloid development. Homeobox C6 (HOXC6) emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction
western blot (WB) and immunohistochemistry. Subsequently
the effects of downregulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8
flow cytometry
transwell migration and WB assays. Meanwhile
we performed transcriptome sequencing and gene set enrichment analysis (GSEA) to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments.ResultsHOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs. Downregulation of HOXC6 inhibited proliferation
migration and extracellular matrix (ECM) accumulation and promoted KF apoptosis. GSEA predicted that the hypoxia signaling pathway was associated with HOXC6 in KFs. Transcriptome sequencing suggested that the extracellular regulated protein kinase (ERK) pathway was one of the downstream pathways of HOXC6 in KFs. Our experiments confirmed that hypoxia-inducible factor-1α (HIF-1α) upregulates HOXC6
contributing to KFs proliferation
migration
apoptosis inhibition and collagen accumulation through the ERK signaling pathway.ConclusionsOur findings first revealed that HOXC6 acts as an oncogenic driver in the molecular mechanisms of fibroblasts in keloids. The HIF-1α/HOXC6/ERK axis promotes proliferation
migration and ECM production by KFs
contributing to the progression of keloids. Taken together
HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.
关键词
Keywords
KeloidFibroblastHOXC6HIF-1αERKTranscriptome
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