The mammalian main olfactory epithelium (MOE) is exposed to a wide spectrum of external chemicals during respiration and relies on adaptive plasticity to maintain its structural and functional integrity. We previously reported that the chemo-responsive and cholinergic transient receptor potential channel M5 (TRPM5)-expressing-microvillous cells (MCs) in the MOE are required for maintaining odor-evoked electrophysiological responses and olfactory-guided behavior during two-week exposure to an inhaled chemical mixture. Here, we investigated the underlying factors by assessing the potential modulatory effects of TRPM5-MCs on MOE morphology and cell proliferation and apoptosis, which are important for MOE maintenance. In the posterior MOE of TRPM5-GFP mice, we found that two-week chemical exposure induced a significant increase in Ki67-expressing proliferating basal stem cells without a significant reduction in the thickness of the whole epithelium or mature olfactory sensory neuron (OSN) layer. This adaptive increase in stem cell proliferation was missing in chemical-exposed transcription factor Skn-1a knockout (Skn-1a-/-) mice lacking TRPM5-MCs. In addition, a greater number of isolated OSNs from chemical-exposed Skn-1a-/- mice displayed unhealthily high levels of resting intracellular Ca2+. Intriguingly, in the anterior MOE where we found a higher density of TRPM5-MCs, chemical-exposed TRPM5-GFP mice exhibited a time-dependent increase in apoptosis and a loss of mature OSNs without a significant increase in proliferation or neurogenesis to compensate for OSN loss. Together, our data suggest that TRPM5-MC-dependent region-specific upregulation of cell proliferation in the majority of the MOE during chemical exposure contributes to the adaptive maintenance of OSNs and olfactory function.

中文翻译：

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表达 TRPM5 的微绒毛细胞在化学暴露期间调节区域特异性细胞增殖和凋亡。

哺乳动物的主要嗅觉上皮 (MOE) 在呼吸过程中暴露于多种外部化学物质，并依靠适应性可塑性来维持其结构和功能的完整性。我们之前报道过，MOE 中的化学反应和胆碱能瞬时受体电位通道 M5 (TRPM5) 表达微绒毛细胞 (MCs) 是在两周暴露于吸入化学混合物。在这里，我们通过评估 TRPM5-MCs 对 MOE 形态和细胞增殖和凋亡的潜在调节作用来研究潜在因素，这对 MOE 维持很重要。在 TRPM5-GFP 小鼠的后部 MOE 中，我们发现两周的化学暴露诱导表达 Ki67 的增殖性基底干细胞显着增加，而整个上皮或成熟嗅觉感觉神经元 (OSN) 层的厚度没有显着降低。这种干细胞增殖的适应性增加在缺乏 TRPM5-MCs 的化学暴露转录因子 Skn-1a 敲除 (Skn-1a-/-) 小鼠中缺失。此外，来自化学暴露的 Skn-1a-/- 小鼠的大量分离的 OSN 显示出不健康的高水平静息细胞内 Ca2+。有趣的是，在我们发现更高密度的 TRPM5-MCs 的前部 MOE 中，化学暴露的 TRPM5-GFP 小鼠表现出随时间变化的细胞凋亡增加和成熟 OSNs 的丧失，而增殖或神经发生没有显着增加以补偿 OSN失利。一起，