Porras-Gonzalez C, Palacios-Garcia J M, Sanchez-Gomez S, Maza-Solano J M, Alba G, Sanchez-Margalet V, Palomares O, Del Cuvillo A, Cordero-Varela J A, Moreno-Luna R, Munoz-Bravo J L
Rhinology Unit, Department of Otolaryngology, Head and Neck Surgery, Virgen Macarena University Hospital/FISEVI, Seville, Spain; Institute of Biomedicine of Seville (IBiS), Virgen del Rocio, University of Seville, CSIC, Seville, Spain.
Rhinology Unit, Department of Otolaryngology, Head and Neck Surgery, Virgen Macarena University Hospital/FISEVI, Seville, Spain.
Rhinology. 2023 Apr 1;61(2):180-189. doi: 10.4193/Rhin22.309.
Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed. We aimed to elucidate whether fibroblasts could have a role in the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP).
We performed whole-transcriptome microarray in fibroblast cultured from CRSwNP samples and confirmed our results by qRT-PCR. We selected patients without other associated diseases in upper airway. To investigate shifts in transcriptional profile we used fibroblasts from nasal polyps and uncinate mucosae from patient with CRSwNP, and fibroblasts from uncinate mucosae from healthy subjects as controls.
This study exposes activation of a pro-inflammatory and pro-fibrotic transcriptional program in nasal polyps and CRSwNP fibroblasts when compared to controls. Our Gene-set Enrichment Analysis (GSEA) pointed to common up-regulation of several pro-inflammatory pathways in patients-derived fibroblasts, along with higher mRNA expression levels of cytokines, growth factors and extracellular matrix components.
Our work reveals a potential new source of inflammatory signaling in CRSwNP. Furthermore, our results suggest that deregulated inflammatory signaling in tissue-resident fibroblasts could support a Type-2 inflammatory response. Further investigations will be necessary to demonstrate the functionality of these novel results.
成纤维细胞和其他间充质细胞最近被确定为引发组织特异性炎症反应的关键细胞。成纤维细胞炎症程序的持续激活被认为是多种组织和病理中慢性炎症的潜在原因。然而，成纤维细胞在上气道慢性炎症发生中的作用此前尚未得到探讨。我们旨在阐明成纤维细胞在伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）的炎症反应中是否起作用。
我们对从CRSwNP样本培养的成纤维细胞进行了全转录组微阵列分析，并通过qRT-PCR证实了我们的结果。我们选择了上气道无其他相关疾病的患者。为了研究转录谱的变化，我们使用了来自CRSwNP患者鼻息肉和钩突黏膜的成纤维细胞，以及来自健康受试者钩突黏膜的成纤维细胞作为对照。
与对照组相比，本研究揭示了鼻息肉和CRSwNP成纤维细胞中促炎和促纤维化转录程序的激活。我们的基因集富集分析（GSEA）指出，患者来源的成纤维细胞中几种促炎途径普遍上调，同时细胞因子、生长因子和细胞外基质成分的mRNA表达水平更高。
我们的研究揭示了CRSwNP中炎症信号的一个潜在新来源。此外，我们的结果表明，组织驻留成纤维细胞中失调的炎症信号可能支持2型炎症反应。需要进一步研究来证明这些新结果的功能。
