Integrated bioinformatics analysis and experimental validation identifies CPE as a potential biomarker and therapeutic target for skin aging.
Xiaozhen PengYun ZhongRui MaoFanping HeYufan ChengMengting ChenLei ZhouHongfu XieJi LiYiya ZhangPublished in: Experimental dermatology (2024)
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 H 2 O 2 -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.
Keyphrases
- wound healing
- high glucose
- endothelial cells
- single cell
- network analysis
- genome wide
- diabetic rats
- machine learning
- soft tissue
- rna seq
- oxidative stress
- cell proliferation
- poor prognosis
- gene expression
- randomized controlled trial
- dna damage
- induced apoptosis
- bioinformatics analysis
- high throughput
- stress induced
- magnetic resonance imaging
- dna methylation
- transcription factor
- computed tomography
- endoplasmic reticulum stress
- induced pluripotent stem cells
- data analysis