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Neuropeptides regulate embryonic salivary gland branching through the FGF / FGFR pathway in aging klotho‐deficient mice

Year: 2024
Type: article
Abstract: Salivary gland branching morphogenesis is regulated by the functional integration of neuronal signaling, but the underlying mechanisms are not fully understood in aging accelerated klotho‐deficient (Kl−/−) mice. Here, we investigated whether the neuropeptides substance P (SP) and neuropeptide Y (NPY) affect the branching morphogenesis of embryonic salivary glands in aging Kl−/− mice. In the salivary glands of embryonic Kl−/− mice, morphological analysis and immunostaining revealed that epithelial bud formation, neuronal cell proliferation/differentiation, and the expression of the salivary gland functional marker ZO‐1 were decreased in embryonic ductal cells. Incubation with SP/NPY at E12‐E13d promoted branching morphogenesis, parasympathetic innervation, and epithelial proliferation in salivary glands of embryonic Kl−/− mice. The ERK inhibitor U0126 specifically inhibited neuronal substance‐induced epithelial bud formation in the embryonic salivary gland. RNA‐seq profiling analysis revealed that the expression of fibroblast growth factors/fibroblast growth factors (FGFs/FGFRs) and their receptors was significantly regulated by SP/NPY treatment in the embryonic salivary gland (E15). The FGFR inhibitor BGJ389 inhibited new branching formation induced by SP and NPY treatment and ERK1/2 expression. These results showed that aging may affect virtually the development of salivary gland by neuronal dysfunction. The neuropeptides SP/NPY induced embryonic salivary gland development through FGF/FGFR/ERK1/2‐mediated signaling.
Source: Aging Cell
DOI: 10.1111/acel.14329
Language: English
Subfield: Physiology
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,350
OpenAlex ID: W4402312859
FWCI: 1.196
Cites: 76
Cited by: 5
Related to: 10