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

ABSTRACT 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.