After severe tissue injury, HBCs are activated and transited to GBCs, leading to the regeneration of various cell types constituting the OE ( Schnittke et al., 2015 Gadye et al., 2017 Schwob et al., 2017). Mitotically active globose basal cells (GBCs) continuously generate OSNs throughout life ( Schwob et al., 2017), while dormant horizontal basal cells (HBCs) adherent to the basal lamina do not contribute to the maintenance of normal OE ( Leung et al., 2007). The olfactory epithelium (OE) is a pseudostratified epithelial structure mainly composed of supporting cells, olfactory sensory neurons (OSNs), and progenitors/basal cells ( Schwob, 2002). This study reveals an important role of supporting cells in OE regeneration and provides a critical link between Ym2 and inflammation in this process. Moreover, anti-inflammatory treatment reduces Ym2 expression and delays OE regeneration, which are counteracted by Ym2 overexpression. Here we report that OE injury causes upregulation of a chitinase-like protein, Ym2, in supporting cells, which facilitates OE regeneration. How supporting cells contribute to this process is not entirely understood. SIGNIFICANCE STATEMENT The mammalian olfactory epithelium (OE) is a unique neural tissue that regenerates sensory neurons and nonsensory supporting cells throughout life and postinjury. 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. 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. Similarly, Ym2 bidirectionally regulated cell proliferation and differentiation in OE colonies. Genetic knockdown of Ym2 in supporting cells attenuated recovery of the injured OE, while Ym2 overexpression by lentiviral infection accelerated OE regeneration. We found that Ym2 expression was enhanced in supporting cells after OE injury. 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. How supporting cells contribute to OE regeneration remains largely unknown. The adult olfactory epithelium (OE) regenerates sensory neurons and nonsensory supporting cells from resident stem cells after injury.
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