关键词: Chronic rhinosinusitis with nasal polyps (CRSwNP) Eosinophils (EOS) Epithelial–mesenchymal transition (EMT) Hedgehog (Hh) PTCH Proliferation

Mesh : Humans Hedgehog Proteins Nasal Polyps / pathology Rhinitis / pathology Epithelial-Mesenchymal Transition / physiology Sinusitis / pathology Cell Proliferation Signal Transduction Chronic Disease

来  源:   DOI:10.1007/s00405-022-07664-5

Abstract:
OBJECTIVE: To investigate the pathogenesis of the hedgehog (Hh) signaling pathway activated by inflammation in the development of chronic rhinosinusitis with nasal polyps (CRSwNP).
METHODS: The 82 people including CRSwNP patients (case group) and nasal septal deviation patients (control group) were recruited. The samples in the case group were collected and classified into two groups: mucosal tissue of nasal polyps (NP group) and mucosal tissue adjacent to nasal polyps (NM group), the samples were collected from the control group as CM group. Clinical characteristics were assessed. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were performed to detect eosinophils (EOS), the expression of the key genes of the pathway and epithelial-mesenchymal transition (EMT) markers in the samples.
RESULTS: There were significant differences in the nasal obstruction visual analog scale (VAS) score, rhinorrhea VAS score, percentage of blood EOS, blood EOS absolute counts and tissue EOS counts in the case group compared with the control group (P < 0.05). The EOS level and expression levels of PTCH1, SMO, Gli1, Gli2, Ki67 and vimentin were higher in NP group than in the other two groups (P < 0.05). E-cadherin expression was decreased in NP group (P < 0.05). A positive correlation between PTCH1 expression and CRSwNP Lund-Mackay score in NP group.
CONCLUSIONS: Our results indicated that the activation of Hh signaling pathway might promote cell proliferation and EMT occurrence, ultimately leading to the development of CRSwNP, which might provide a new target for treatment.
摘要:
目的:探讨炎症激活的Hedgehog(Hh)信号通路在慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)发生发展中的作用机制。
方法:纳入82人,包括CRSwNP患者(病例组)和鼻中隔偏曲患者(对照组)。收集病例组标本,分为鼻息肉黏膜组织(NP组)和鼻息肉旁黏膜组织(NM组),样本取自对照组作为CM组。评估临床特征。苏木素和伊红(H&E)和免疫组织化学(IHC)染色检测嗜酸性粒细胞(EOS),该途径的关键基因和上皮-间质转化(EMT)标记在样品中的表达。
结果:鼻塞视觉模拟量表(VAS)评分存在显着差异,鼻漏VAS评分,血液EOS的百分比,病例组血EOS绝对计数和组织EOS计数与对照组比较(P<0.05)。PTCH1、SMO、NP组Gli1、Gli2、Ki67和波形蛋白均高于其他两组(P<0.05)。NP组E-cadherin表达降低(P<0.05)。NP组PTCH1表达与CRSwNPLund-Mackay评分呈正相关。
结论:我们的结果表明,Hh信号通路的激活可能促进细胞增殖和EMT的发生,最终导致CRSwNP的发展,这可能为治疗提供新的目标。
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