Matsumoto Naoyuki, Ueha Satoshi, Ueha Rumi, Koyama Misaki, Yamakawa Kaoru, Sato Taku, Goto Takao, Kono Takeyuki, Shichino Shigeyuki, Matsushima Kouji, Kondo Kenji
Department of Otolaryngology and Head and Neck Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Division of Molecular Regulation of Inflammation and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
Laryngoscope. 2025 Oct;135(10):3732-3739. doi: 10.1002/lary.32325. Epub 2025 Jun 7.
Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV) types 6 and 11. However, the cellular and molecular mechanisms underlying its pathogenesis remain to be elucidated. Recently, the conditional reprogramming (CR) method, which reprograms epithelial cells to an undifferentiated stem cell state, has been shown to be effective for studying RRP. Here, we investigated the relationship between viral and host gene expression in CR cells and explored the molecular pathogenesis of RRP.
We evaluated the passage capacity and growth rate of CR cells from fresh RRP tissues and adjacent normal tissues from patients with RRP. Furthermore, we performed RNA-seq analysis of CR cells across multiple passages to characterize the gene expression profiles associated with RRP.
RRP-derived CR cells exhibited greater passage capacity and proliferation rates than adjacent normal tissue-derived CR cells. HPV6 gene was expressed in all RRP-derived CR cells and its expression decreased with each passage. We identified three categories of genes correlated with HPV6: inflammatory genes (e.g., CTSS, CFB), oncogenic genes (e.g., CEACAM5, CEACAM6), and glycosylation-related genes (e.g., ST6GALNAC1, FUT2).
HPV6-induced gene expression signature in infected epithelial cells may play a role in RRP pathogenesis. Further molecular investigations are necessary to determine whether controlling these genes and related factors can control the progression of RRP.
N/A.
复发性呼吸道乳头状瘤病（RRP）由6型和11型人乳头瘤病毒（HPV）引起。然而，其发病机制的细胞和分子机制仍有待阐明。最近，将上皮细胞重编程为未分化干细胞状态的条件重编程（CR）方法已被证明对研究RRP有效。在此，我们研究了CR细胞中病毒和宿主基因表达之间的关系，并探讨了RRP的分子发病机制。
我们评估了来自RRP患者新鲜RRP组织和相邻正常组织的CR细胞的传代能力和生长速率。此外，我们对多代CR细胞进行了RNA测序分析，以表征与RRP相关的基因表达谱。
RRP来源的CR细胞比相邻正常组织来源的CR细胞表现出更大的传代能力和增殖速率。HPV6基因在所有RRP来源的CR细胞中均有表达，且其表达随传代次数的增加而降低。我们鉴定出与HPV6相关的三类基因：炎症基因（如CTSS、CFB）、致癌基因（如CEACAM5、CEACAM6）和糖基化相关基因（如ST6GALNAC1、FUT2）。
HPV6在受感染上皮细胞中诱导的基因表达特征可能在RRP发病机制中起作用。需要进一步的分子研究来确定控制这些基因和相关因子是否可以控制RRP的进展。
无。
