Xu Xinya, Lu Xinhua, Chen Xinling, Yao Amin, Lai Wei
Department of Dermatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Department of Neurosurgery, Foresea Life Insurance Guangzhou General Hospital, Guangzhou, China.
J Cosmet Dermatol. 2025 Apr;24(4):e70098. doi: 10.1111/jocd.70098.
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.
To investigate the expression, clinical significance, and mechanism of CD47 in photoaging.
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.
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.
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.
CD47可负向调节巨噬细胞介导的吞噬作用，并促使衰老细胞在衰老过程中积累。然而，CD47在光老化皮肤中是否过表达以及是否参与光老化发病机制仍不清楚。
研究CD47在光老化中的表达、临床意义及机制。
从老年受试者中收集暴露于阳光的皮肤样本（n = 10）和防晒皮肤样本（n = 10），进行CD47染色，随后分析其与胶原蛋白和弹性蛋白含量以及p16表达的相关性。接着建立细胞光老化模型，检测光老化成纤维细胞中CD47的表达。此外，通过构建共培养系统评估光老化成纤维细胞对巨噬细胞介导的吞噬和清除作用的影响。应用小干扰RNA（SiRNA）阻断CD47/SIRPα轴，以确定其在此过程中的作用。最后，评估皮肤样本中CD47/SIRPα轴的激活情况。
我们发现暴露于阳光的老年皮肤中真皮CD47表达增加，这与胶原蛋白含量降低、弹性蛋白积累增强以及真皮p16表达密切相关。接下来，在暴露于阳光的老年皮肤来源的成纤维细胞和光老化的成纤维细胞中均检测到CD47升高。我们发现光老化的成纤维细胞通过CD47/SIRPα轴损害共培养巨噬细胞的吞噬功能，阻断CD47/SIRPα轴可改善巨噬细胞的清除作用。此外，在暴露于阳光的老年皮肤中发现CD47/SIRPα轴被激活。
本研究首次证明CD47高表达并参与介导光老化成纤维细胞的积累，为CD47作为光老化的潜在生物标志物和治疗靶点提供了重要证据。
