Abstract / Summary
Pressure therapy (PT) is a well-established clinical treatment for hypertrophic scars (HS). While its efficacy in reducing scar thickness and hardness is recognized, the specific molecular mechanisms and cellular targets underlying its therapeutic effects remain poorly understood, limiting the optimization of treatment strategies. To address this critical knowledge gap, we employed an unbiased transcriptomic approach to systematically decipher the gene regulatory network modulated by PT. A rabbit ear HS model was established and subjected to PT at 20 mmHg. Comprehensive transcriptomic profiling via RNA sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs). Subsequent bioinformatics analyses were employed to pinpoint core genes and predict involved pathways. Key findings were validated using RT-qPCR and Western blotting. PT significantly improved scar morphology and histology. Transcriptomic analysis revealed 410 DEGs, with seven hub genes (DKK1, SOST, SMAD7, SMAD3, TGF-β1, COL1A1, MMP1) being centrally implicated. Bioinformatics and experimental validation confirmed that PT specifically upregulates inhibitors (DKK1, SOST, SMAD7) while downregulating fibrotic promoters (SMAD3, TGF-β1, COL1A1, MMP1). This coordinated shift collectively attenuates the pro-fibrotic Wnt/β-catenin and TGF-β/Smad signaling pathways. Our study provides further transcriptome-level insights into PT’s mechanism, revealing it as a regulator that modulates the fibrotic gene network by simultaneously targeting multiple key nodes across two major fibrotic pathways. These findings offer potential novel molecular targets for enhancing scar management.