Integrated bioinformatics analysis and experimental validation identifies CPE as a potential biomarker and therapeutic target for skin aging

IF 3.5 3区医学 Q1 DERMATOLOGY

Experimental Dermatology Pub Date : 2024-06-17 DOI:10.1111/exd.15120

Xiaozhen Peng, Yun Zhong, Rui Mao, Fanping He, Yufan Cheng, Mengting Chen, Lei Zhou, Hongfu Xie, Ji Li, Yiya Zhang

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引用次数: 0

Abstract

Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H₂O₂-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.

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综合生物信息学分析和实验验证确定 CPE 是皮肤老化的潜在生物标志物和治疗靶点。

衰老是一个不可避免的生理过程，其特点是生理功能逐渐衰退。它是一种复杂的自然现象，会导致结构和功能衰退。尽管在了解老化机制方面取得了重大进展，但预测性生物标志物和预防性疗法仍然有限。利用加权基因共表达网络分析（WGCNA）和机器学习技术，我们基于与老化相关的大体转录组和单细胞转录组数据，发现羧肽酶 E（CPE）是皮肤老化的关键标志物。接下来，我们的研究揭示了在复制、UVA 诱导和 H2O2- 诱导的衰老人真皮成纤维细胞（HDFs）中 CPE 的下调。此外，shRNA 介导的 CPE 敲除诱导了 HDFs 的衰老，而 CPE 的过表达延迟了 HDFs 的衰老。此外，下调的 CPE 会抑制胶原蛋白的合成并诱发炎症，这凸显了其作为皮肤老化治疗靶点的潜力。总之，我们的研究表明，CPE 可作为皮肤老化的预测因子和治疗干预的可选靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Dermatology 医学-皮肤病学

CiteScore

6.70

自引率

5.60%

发文量

201

审稿时长

2 months

期刊介绍： Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.