瞬时受体电位香草素 1 和 4 在嗅觉再生中的作用。
The Roles of Transient Receptor Potential Vanilloid 1 and 4 in Olfactory Regeneration.
机构信息
Department of Otorhinolaryngology-Head and Neck Surgery, Wakayama Medical University, Wakayama, Japan.
Department of Human Pathology, Wakayama Medical University, Wakayama, Japan.
出版信息
Lab Invest. 2023 Apr;103(4):100051. doi: 10.1016/j.labinv.2022.100051. Epub 2023 Jan 12.
Olfactory disorders, which are closely related to cognitive deterioration, can be caused by several factors, including infections, such as COVID-19; aging; and environmental chemicals. Injured olfactory receptor neurons (ORNs) regenerate after birth, but it is unclear which receptors and sensors are involved in ORN regeneration. Recently, there has been great focus on the involvement of transient receptor potential vanilloid (TRPV) channels, which are nociceptors expressed on sensory nerves during the healing of damaged tissues. The localization of TRPV in the olfactory nervous system has been reported in the past, but its function there are unclear. Here, we investigated how TRPV1 and TRPV4 channels are involved in ORN regeneration. TRPV1 knockout (KO), TRPV4 KO, and wild-type (WT) mice were used to model methimazole-induced olfactory dysfunction. The regeneration of ORNs was evaluated using olfactory behavior, histologic examination, and measurement of growth factors. Both TRPV1 and TRPV4 were found to be expressed in the olfactory epithelium (OE). TRPV1, in particular, existed near ORN axons. TRPV4 was marginally expressed in the basal layer of the OE. The proliferation of ORN progenitor cells was reduced in TRPV1 KO mice, which delayed ORN regeneration and the improvement of olfactory behavior. Postinjury OE thickness improved faster in TRPV4 KO mice than WT mice but without acceleration of ORN maturation. The nerve growth factor and transforming growth factor ß levels in TRPV1 KO mice were similar to those in WT mice, and the transforming growth factor ß level was higher than TRPV4 KO mice. TRPV1 was involved in stimulating the proliferation of progenitor cells. TRPV4 modulated their proliferation and maturation. ORN regeneration was regulated by the interaction between TRPV1 and TRPV4. However, in this study, TRPV4 involvement was limited compared with TRPV1. To our knowledge, this is the first study to demonstrate the involvement of TRPV1 and TRPV4 in OE regeneration.
嗅觉障碍与认知功能恶化密切相关，可由多种因素引起，包括感染（如 COVID-19）、衰老和环境化学物质等。出生后，受伤的嗅觉受体神经元（ORNs）会再生，但目前尚不清楚哪些受体和传感器参与了 ORN 再生。最近，人们非常关注瞬时受体电位香草酸（TRPV）通道的参与，该通道在受损组织愈合过程中表达于感觉神经上的伤害感受器。过去曾有报道 TRPV 在前嗅神经系统中的定位，但它在那里的功能尚不清楚。在这里，我们研究了 TRPV1 和 TRPV4 通道如何参与 ORN 再生。我们使用甲巯咪唑诱导的嗅觉功能障碍模型，研究 TRPV1 敲除（KO）、TRPV4 KO 和野生型（WT）小鼠中 TRPV1 和 TRPV4 通道的作用。通过嗅觉行为、组织学检查和生长因子测量评估 ORN 再生。结果发现，TRPV1 和 TRPV4 均在前嗅上皮（OE）中表达。特别是 TRPV1 存在于 ORN 轴突附近。TRPV4 在 OE 的基底细胞层中略有表达。TRPV1 KO 小鼠中 ORN 祖细胞的增殖减少，导致 ORN 再生和嗅觉行为改善延迟。与 WT 小鼠相比，TRPV4 KO 小鼠的 OE 厚度在损伤后更快地增加，但 ORN 成熟没有加速。TRPV1 KO 小鼠的神经生长因子和转化生长因子 ß 水平与 WT 小鼠相似，而转化生长因子 ß 水平高于 TRPV4 KO 小鼠。TRPV1 参与刺激祖细胞的增殖。TRPV4 调节它们的增殖和成熟。ORN 再生受 TRPV1 和 TRPV4 之间相互作用的调节。然而，在这项研究中，与 TRPV1 相比，TRPV4 的作用有限。据我们所知，这是首次证明 TRPV1 和 TRPV4 参与 OE 再生的研究。
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