Neuropeptide Y and extracellular signal-regulated kinase mediate injury-induced neuroregeneration in mouse olfactory epithelium

Abstract

In the olfactory epithelium (OE), injury induces ATP release, and subsequent activation of P2 purinergic receptors by ATP promotes neuroregeneration by increasing basal progenitor cell proliferation. The molecular mechanisms underlying ATP-induced increases in OE neuroregeneration have not been established. In the present study, the roles of neuroproliferative factors neuropeptide Y (NPY) and fibroblast growth factor2 (FGF2), and p44/42 extracellular signal-regulated kinase (ERK) on ATP-mediated increases of neuroregeneration in the OE were investigated. ATP increased basal progenitor cell proliferation in the OE via activation of P2 purinergic receptors in vitro and in vivo as monitored by incorporation of 5′-ethynyl-2′-deoxyuridine, a thymidine analog, into DNA, and proliferating cell nuclear antigen (PCNA) protein levels. ATP induced p44/42 ERK activation in globose basal cells (GBC) but not horizontal basal cells (HBC). ATP differentially regulated p44/42 ERK over time in the OE both in vitro and in vivo with transient inhibition (5–15 min) followed by activation (30 min – 1 hr) of p44/42 ERK. In addition, ATP indirectly activated p44/42 ERK in the OE via ATP-induced NPY release and subsequent activation of NPY Y1 receptors in the basal cells. There were no synergistic effects of ATP and NPY or FGF2 on OE neuroregeneration. These data clearly have implications for the pharmacological modulation of neuroregeneration in the olfactory epithelium.

Ascl3 transcription factor marks a distinct progenitor lineage for non-neuronal support cells in the olfactory epithelium

“…In all cases, loss of gene function in the microvillar cells affected proliferation and regenerative ability of the basal progenitor cells. It is proposed that microvillar cells coordinate signals from the external environment, and also release signals that regulate proliferation of the progenitor cells478934. The finding that specific ablation of a cilia gene in the HBCs reduced the number of GBCs and of OSNs after chemically-induced injury supports the idea that the stem and progenitor cells may respond to non-cell autonomous signals derived from cells such as the microvillar cells23.…”

The Role of Pannexin3-Modified Human Dental Pulp-Derived Mesenchymal Stromal Cells in Repairing Rat Cranial Critical-Sized Bone Defects

“…One possible explanation is that Panx3 functions as a hemichannel mediating ATP release from the cytoplasm into extracellular environments [33]. Likewise, extracellular ATP could activate the ERK signaling pathway [34][35][36], partially explaining the promotive implication of Panx3 on the ERK pathway. Certainly, this is unlikely to be the sole mechanism of Panx3-induced upregulation of osteogenic differentiation.…”

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

“…It seems that dinucleoside play an important role in the progression of the pathology, since the Ap 4 A and Ap 5 A concentration increases with age, being higher in patients over 40 years of age than in younger aniridia patients. It has been demonstrated that P2 purinergic receptors are associated with differentiation, proliferation and neurogenesis in neonatal and adult mouse olfactory epithelium (Jia and Hegg, 2012). In the corneal epithelium the cell proliferation process is initiated by P2Y 2 receptor activation via the ERK1/2 pathway (Muscella et al, 2004).…”