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免疫组织化学分析原发性和复发性翼状胬肉上皮组织中 HIF1α 和 HIF2α 的免疫反应性。

HIF1α and HIF2α immunoreactivity in epithelial tissue of primary and recurrent pterygium by immunohistochemical analysis.

机构信息

Eye Center, Medical Center - University of Freiburg, Killianstraße 5, 79106, Freiburg, Germany.

出版信息

Int Ophthalmol. 2023 Dec;43(12):4551-4562. doi: 10.1007/s10792-023-02855-3. Epub 2023 Sep 8.

Abstract

PURPOSE

Hypoxia-inducible factors (HIFs) are considered to play a significant role in the pathogenesis of pterygium. The aim of this study was to investigate the relative expression or immunoreactivity of HIF1α and HIF2α in the epithelium of primary pterygium, recurrences and healthy conjunctiva.

METHODS

Immunohistochemical staining was performed with antibodies against HIF1α and HIF2α, respectively, on 55/84 primary pterygium specimens, 6/28 recurrences and 20/20 control tissues (healthy conjunctiva).

RESULTS

Immunohistochemical staining revealed lower epithelial immunoreactivity of HIF1α and HIF2α in both primary pterygium (11% and 38%) and recurrences (18% and 21%) when compared to healthy conjunctival tissue (46% and 66%). Differences between immunoreactivity of HIF1α and of HIF2α in primary pterygium and controls were each highly significant (p < .001). Within the group of primary pterygium, epithelial immunoreactivity of HIF2α (38%) was significantly higher than that of HIF1α (11%). In recurrent pterygium and healthy conjunctiva, immunoreactivity levels of HIF2α were higher than those of HIF1α as well; however, differences between both isoforms were not significant.

CONCLUSION

Our study shows evidence that the higher expressed epithelial HIF2α, rather than HIF1α, and the balance between both HIF isoforms might be relevant factors associated with pathogenesis of primary pterygium. Modulation of HIF2α levels and activity may thus offer a new therapeutic approach to the treatment of advancing pterygium where the initial stage with its HIF1-peak has already passed.

摘要

目的

缺氧诱导因子(HIFs)被认为在翼状胬肉的发病机制中起重要作用。本研究旨在研究 HIF1α 和 HIF2α 在原发性翼状胬肉、复发和健康结膜的上皮中的相对表达或免疫反应性。

方法

使用针对 HIF1α 和 HIF2α 的抗体分别对 55/84 例原发性翼状胬肉标本、6/28 例复发和 20/20 例对照组织(健康结膜)进行免疫组织化学染色。

结果

与健康结膜组织(46%和 66%)相比,原发性翼状胬肉(11%和 38%)和复发(18%和 21%)的上皮 HIF1α 和 HIF2α 免疫反应性较低。HIF1α 和 HIF2α 在原发性翼状胬肉和对照组之间的免疫反应性差异均具有高度显著性(p<0.001)。在原发性翼状胬肉组中,HIF2α 的上皮免疫反应性(38%)明显高于 HIF1α(11%)。在复发的翼状胬肉和健康结膜中,HIF2α 的免疫反应性水平也高于 HIF1α;然而,两种同工型之间的差异并不显著。

结论

我们的研究表明,高表达的上皮 HIF2α,而不是 HIF1α,以及两种 HIF 同工型之间的平衡可能是与原发性翼状胬肉发病机制相关的重要因素。因此,调节 HIF2α 水平和活性可能为治疗已经通过其 HIF1-峰值的初始阶段的进展性翼状胬肉提供新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5d9/10724320/04283e2b753a/10792_2023_2855_Fig1_HTML.jpg

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