Fibronectin in the olfactory mucus increases sensitivity of olfactory receptor response to odorants

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-05-14 DOI:10.1126/sciadv.adu7271

Stella Chapman, Kenji Kondo, Sayoko Ihara, Chiori Ijichi, Kazushige Touhara, Koji Sato

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Abstract

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.

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嗅觉粘液中的纤维连接蛋白增加了嗅觉受体对气味反应的敏感性

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然知之甚少。在陆生脊椎动物中，吸入的气味通过嗅上皮粘液（OEM）扩散，然后激活嗅觉感觉神经元上的嗅觉受体（ORs）并启动腺苷3 ',5 ' -单磷酸腺苷（cAMP）介导的信号传导。在人和小鼠中，OEM分泌受损与嗅觉敏感性受损有关，但OEM是否直接改善敏感性以及是否存在特定的活性因子尚不清楚。在这里，使用基于cAMP成像的异种OR表达实验，我们证明了来自人类OEM的纤维连接蛋白增加了OR对气味反应的敏感性。纤维连接蛋白的应用部分恢复了OEM去除后小鼠嗅上皮的电嗅觉反应。在人类中，特发性嗅觉障碍患者的OEM纤维连接蛋白水平显著降低。这些发现揭示了OEM纤维连接蛋白在嗅觉中的作用，并可能导致嗅觉传感器的敏感性增强添加剂和低氧治疗。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.