Thrombospondin-1 (TSP1) is the prototypical member of a family of secreted proteins that modulate cell behavior by engaging with molecules in the extracellular matrix and with receptors on the cell surface. CD47 is widely displayed on many, if not all, cell types and is a high affinity TSP1 receptor. CD47 is a self-antigen that limits innate immune cell activities, a feature recently exploited to enhance cancer immunotherapy. Another major role for CD47 in health and disease is to mediate TSP1 signaling. TSP1 acting through CD47 contributes to mitochondrial, metabolic and endocrine dysfunction. Studies in animal models found that elevated TSP1 expression, acting in part through CD47, causes mitochondrial and metabolic dysfunction. Clinical studies established that abnormal TSP1 expression positively correlates with obesity, fatty liver disease and diabetes. The unabated increase in these conditions worldwide and the availability of CD47 targeting drugs justify a closer look into how TSP1 and CD47 disrupt metabolic balance and the potential for therapeutic intervention.

中文翻译：

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CD47 和血小板反应蛋白-1 对线粒体、代谢和糖尿病的调节

血小板反应蛋白-1 (TSP1) 是分泌蛋白家族的原型成员，通过与细胞外基质中的分子和细胞表面的受体结合来调节细胞行为。CD47 广泛存在于许多（如果不是全部）细胞类型上，并且是一种高亲和力的 TSP1 受体。CD47 是一种自身抗原，可以限制先天免疫细胞的活动，这是最近被用来增强癌症免疫治疗的一个特征。CD47 在健康和疾病中的另一个主要作用是介导 TSP1 信号。通过 CD47 起作用的 TSP1 导致线粒体、代谢和内分泌功能障碍。动物模型研究发现，TSP1 表达升高，部分通过 CD47 起作用，导致线粒体和代谢功能障碍。临床研究证实异常 TSP1 表达与肥胖呈正相关，脂肪肝和糖尿病。这些疾病在全球范围内的持续增加以及 CD47 靶向药物的可用性证明了仔细研究 TSP1 和 CD47 如何破坏代谢平衡和治疗干预的潜力是合理的。