Chapman Stella, Kondo Kenji, Ihara Sayoko, Ijichi Chiori, Sato Koji, Touhara Kazushige
Laboratory of Biological Chemistry, Department of Applied Biological Chemistry, The University of Tokyo, Tokyo 113-8657, Japan.
Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
Sci Adv. 2025 May 16;11(20):eadu7271. doi: 10.1126/sciadv.adu7271. Epub 2025 May 14.
Olfaction is a highly sensitive chemical detection system, but the origins of this sensitivity remain poorly understood. In terrestrial vertebrates, inhaled odorants diffuse through olfactory epithelial mucus (OEM) before activating olfactory receptors (ORs) on olfactory sensory neurons and initiating adenosine 3',5'-monophosphate (cAMP)-mediated signaling. Impaired OEM secretion is associated with impaired olfactory sensitivity in humans and mice, but it remains unclear whether OEM directly improves sensitivity and whether specific active factors exist. Here, using a cAMP imaging-based heterologous OR expression assay, we demonstrate that fibronectin from human OEM increases the sensitivity of OR response to odorant. Fibronectin application partially restores electrical olfactory response of the mouse olfactory epithelium after OEM removal. In humans, OEM fibronectin levels are significantly decreased in patients with idiopathic olfactory disorder. These findings shed light on the role of OEM fibronectin in olfaction and may lead to sensitivity-enhancing additives for odorant sensors and treatments for hyposmia.
嗅觉是一种高度敏感的化学检测系统，但这种敏感性的起源仍知之甚少。在陆生脊椎动物中，吸入的气味分子在激活嗅觉感觉神经元上的嗅觉受体（OR）并启动3',5'-环磷酸腺苷（cAMP）介导的信号传导之前，会通过嗅觉上皮黏液（OEM）扩散。人类和小鼠中OEM分泌受损与嗅觉敏感性受损有关，但尚不清楚OEM是否直接提高敏感性以及是否存在特定的活性因子。在这里，我们使用基于cAMP成像的异源OR表达测定法，证明来自人类OEM的纤连蛋白可提高OR对气味分子反应的敏感性。去除OEM后，应用纤连蛋白可部分恢复小鼠嗅觉上皮的电嗅觉反应。在人类中，特发性嗅觉障碍患者的OEM纤连蛋白水平显著降低。这些发现揭示了OEM纤连蛋白在嗅觉中的作用，并可能导致用于气味传感器的敏感性增强添加剂和嗅觉减退的治疗方法。
