Elevated CD47 Expression Impairs Elimination of Photoaged Fibroblasts by Macrophages and Serves as a Potential Biomarker for Photoaging

BACKGROUND: CD47 could negatively regulate macrophage-mediated phagocytosis and contribute to senescent cells accumulation in aging. However, it remains unknown whether CD47 is overexpressed in photoaged skin and involved in photoaging pathogenesis. AIMS: To investigate the expression, clinical significance, and mechanism of CD47 in photoaging. METHODS: Sun-exposed (n = 10) and sun-protected (n = 10) skin samples were collected from elderly subjects and stained for CD47, and its association with collagen and elastin content and p16 expression was subsequently analyzed. A cellular photoaging model was then established to examine CD47 expression in photoaged fibroblasts. Furthermore, the influence of photoaged fibroblasts on macrophage-mediated phagocytosis and elimination was assessed by constructing a co-culture system. SiRNA was applied to block the CD47/SIRPα axis to determine its role in this process. Finally, the activation of the CD47/SIRPα axis was evaluated in skin samples. RESULTS: We showed the increased dermal CD47 expression in sun-exposed aged skin, which was closely correlated with the reduced collagen content and enhanced elastin accumulation and dermal p16 expression. Next, elevated CD47 was detected in both sun-exposed aged skin-derived fibroblasts and photoaged ones. We discovered that photoaged fibroblasts impaired the phagocytotic function of co-cultured macrophages via CD47/SIRPα axis, and blocking the CD47/SIRPα axis could improve their elimination. Moreover, the CD47/SIRPα axis was found to be activated in the sun-exposed aged skin. CONCLUSIONS: The present study demonstrated for the first time that CD47 was highly expressed and involved in mediating photoaged fibroblasts accumulation, providing important evidence for CD47 as a potential biomarker and therapeutic target for photoaging.