Chitinase-like Protein Ym2 (Chil4) Regulates Regeneration of the Olfactory Epithelium via Interaction with Inflammation
Chitinase-like Protein Ym2 (Chil4) Regulates Regeneration of the Olfactory Epithelium via Interaction with Inflammation
复制标题
几丁质酶样蛋白 Ym2 (Chil4) 通过与炎症的相互作用调节嗅上皮的再生
DOI：
10.1523/jneurosci.1601-20.2021
复制
发表时间：
2021-06-30
影响因子：
5.3
通讯作者：
Yu，Yiqun
中科院分区：
文献类型：
--
作者：
Wang，Li;Ren，Wenwen;Yu，Yiqun
成体嗅觉上皮（OE）在受伤后从常驻干细胞中再生感觉神经元和非感觉支持细胞。支持细胞如何促进 OE 再生仍然很大程度上未知。在这项研究中，我们阐明了 Ym2（也称为 Chil4 或 Chi3l4）（一种在支持细胞中表达的几丁质酶样蛋白）在调节雄性和雌性小鼠体内受损 OE 再生以及体外 OE 集落中细胞增殖/分化中的新作用。我们发现 OE 损伤后支持细胞中 Ym2 表达增强。支持细胞中 Ym2 的基因敲除减弱了受损 OE 的恢复，而慢病毒感染引起的 Ym2 过度表达则加速了 OE 的再生。类似地，Ym2 双向调节 OE 集落中的细胞增殖和分化。此外，抗炎治疗可降低 Ym2 表达并延迟体内 OE 再生和体外细胞增殖/分化，而 Ym2 过表达可抵消这些作用。总的来说，这项研究揭示了 Ym2 通过与炎症反应相互作用在 OE 再生和 OE 集落的细胞增殖/分化中的新作用，为支持细胞在这些过程中的功能提供了新的线索。意义声明 哺乳动物嗅觉上皮 (OE) 是一种独特的神经组织，可在整个生命周期和受伤后再生感觉神经元和非感觉支持细胞。支持细胞如何参与这一过程尚不完全清楚。在这里，我们报告 OE 损伤会导致支持细胞中几丁质酶样蛋白 Ym2 的上调，从而促进 OE 再生。此外，抗炎治疗会降低 Ym2 表达并延迟 OE 再生，而 Ym2 过度表达会抵消这种作用。这项研究揭示了支持细胞在 OE 再生中的重要作用，并在此过程中提供了 Ym2 与炎症之间的关键联系。
The adult olfactory epithelium (OE) regenerates sensory neurons and nonsensory supporting cells from resident stem cells after injury. How supporting cells contribute to OE regeneration remains largely unknown. In this study, we elucidated a novel role of Ym2 (also known as Chil4 or Chi3l4), a chitinase-like protein expressed in supporting cells, in regulating regeneration of the injured OE in vivo in both male and female mice and cell proliferation/differentiation in OE colonies in vitro. We found that Ym2 expression was enhanced in supporting cells after OE injury. Genetic knockdown of Ym2 in supporting cells attenuated recovery of the injured OE, while Ym2 overexpression by lentiviral infection accelerated OE regeneration. Similarly, Ym2 bidirectionally regulated cell proliferation and differentiation in OE colonies. Furthermore, anti-inflammatory treatment reduced Ym2 expression and delayed OE regeneration in vivo and cell proliferation/differentiation in vitro, which were counteracted by Ym2 overexpression. Collectively, this study revealed a novel role of Ym2 in OE regeneration and cell proliferation/differentiation of OE colonies via interaction with inflammatory responses, providing new clues to the function of supporting cells in these processes. SIGNIFICANCE STATEMENT The mammalian olfactory epithelium (OE) is a unique neural tissue that regenerates sensory neurons and nonsensory supporting cells throughout life and postinjury. How supporting cells contribute to this process is not entirely understood. Here we report that OE injury causes upregulation of a chitinase-like protein, Ym2, in supporting cells, which facilitates OE regeneration. Moreover, anti-inflammatory treatment reduces Ym2 expression and delays OE regeneration, which are counteracted by Ym2 overexpression. This study reveals an important role of supporting cells in OE regeneration and provides a critical link between Ym2 and inflammation in this process.