神经营养因子信号传导是辐射后唾液功能障碍的核心机制，它会破坏肌上皮细胞。
Neurotrophin signaling is a central mechanism of salivary dysfunction after irradiation that disrupts myoepithelial cells.
作者信息
Chibly Alejandro M, Patel Vaishali N, Aure Marit H, Pasquale Mary C, Martin Gemma E, Ghannam Mousa, Andrade Julianne, Denegre Noah G, Simpson Colleen, Goldstein David P, Liu Fei-Fei, Lombaert Isabelle M A, Hoffman Matthew P
机构信息
Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Otolaryngology-Head & Neck Surgery, Princess Margaret Cancer Center, Toronto, ON, M5G 2C4, Canada.
出版信息
NPJ Regen Med. 2023 Mar 25;8(1):17. doi: 10.1038/s41536-023-00290-7.
The mechanisms that prevent regeneration of irradiated (IR) salivary glands remain elusive. Bulk RNAseq of IR versus non-IR human salivary glands showed that neurotrophin signaling is highly disrupted post-radiation. Neurotrophin receptors (NTRs) were significantly upregulated in myoepithelial cells (MECs) post-IR, and single cell RNAseq revealed that MECs pericytes, and duct cells are the main sources of neurotrophin ligands. Using two ex vivo models, we show that nerve growth factor (NGF) induces expression of MEC genes during development, and upregulation of NTRs in adult MECs is associated with stress-induced plasticity and morphological abnormalities in IR human glands. As MECs are epithelial progenitors after gland damage and are required for proper acinar cell contraction and secretion, we propose that MEC-specific upregulation of NTRs post-IR disrupts MEC differentiation and potentially impedes the ability of the gland to regenerate.
阻止受辐照唾液腺再生的机制仍不清楚。对受辐照与未受辐照的人类唾液腺进行的大量RNA测序表明，辐射后神经营养因子信号传导受到严重破坏。受辐照后，肌上皮细胞（MEC）中的神经营养因子受体（NTR）显著上调，单细胞RNA测序显示MEC、周细胞和导管细胞是神经营养因子配体的主要来源。使用两种体外模型，我们发现神经生长因子（NGF）在发育过程中诱导MEC基因的表达，成年MEC中NTR的上调与应激诱导的可塑性以及受辐照人类腺体的形态异常有关。由于MEC是腺体损伤后的上皮祖细胞，并且是腺泡细胞正常收缩和分泌所必需的，我们提出受辐照后MEC特异性上调NTR会破坏MEC分化，并可能阻碍腺体的再生能力。
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