Transcriptomic responses of skin to different micro-injury modalities: fire filiform needling, ablative fractional CO2 laser, and filiform needling

Abstract Repair strategies predicated on controlled micro-injury are widely applied in dermatology; however, the distinct molecular cascades initiated by different injury modalities remain incompletely characterized. To systematically delineate and compare the acute transcriptomic landscapes of mouse skin following fire filiform needling (FFN), ablative fractional CO 2 laser (AFCO 2 L), and conventional filiform needling (FN), we performed high-throughput RNA sequencing on dorsal skin samples harvested from C57BL/6J mice one day after treatment with FFN (combining thermal and mechanical stimuli), AFCO 2 L (purely thermal), or FN (purely mechanical). All three interventions disrupted skin barrier integrity and activated canonical injury and repair transcriptional programs. Notably, the two modalities involving thermal stimulation (FFN and AFCO 2 L) elicited a more robust and expansive transcriptomic response than purely mechanical FN, including immune activation, cell proliferation, differentiation, cell migration, metabolic reprogramming, and neurovascular remodeling. Although FFN and AFCO 2 L exhibited broadly convergent transcriptional signatures, key distinctions emerged: FFN was preferentially associated with tissue remodeling, vascular processes, and neural regulation, whereas AFCO 2 L displayed stronger enrichment for immune activation and cell migration. This study provides a comprehensive transcriptomic atlas of acute skin responses to distinct micro-injury modalities and underscores the potent role of thermal stimulation in amplifying dermal repair and remodeling. Our findings establish a systematic framework for understanding the mechanistic underpinnings of micro-injury therapies and for refining their clinical application.