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翼状胬肉患者结膜中 granzyme B 的表达。

Granzyme B Expression in Conjunctiva of Patients with Pterygium.

机构信息

Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC V5Z 3N9, Canada.

出版信息

Int J Mol Sci. 2024 Aug 9;25(16):8679. doi: 10.3390/ijms25168679.

DOI:10.3390/ijms25168679
PMID:39201366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11354738/
Abstract

Pterygium is often associated with chronic ultraviolet (UV) radiation exposure and characterized by the overgrowth of conjunctiva and extracellular matrix (ECM) remodeling. Notably, several studies in the skin have demonstrated that chronic UV radiation can upregulate Granzyme B (GrB) expression and increase ECM degradation. The aim of this study was to compare GrB expression between pterygium and healthy controls and to further link this GrB expression to mast cells. Post-mortem pterygium tissues and conjunctival tissues from age-matched controls were used to assess GrB expression via immunofluorescence and microscopy. We found a significantly higher density of GrB+ cells from pterygium specimens compared to healthy controls. Furthermore, many of the GrB+ cells in pterygium specimens co-expressed tryptase, a mast cell marker. These findings suggest a role for conjunctival mast cell-secreted GrB in the pathogenesis of pterygium and highlight GrB as a possible therapeutic target in delaying or halting pterygium progression.

摘要

翼状胬肉常与慢性紫外线(UV)辐射暴露有关,其特征为结膜和细胞外基质(ECM)重塑过度生长。值得注意的是,皮肤的几项研究表明,慢性 UV 辐射可上调颗粒酶 B(GrB)表达并增加 ECM 降解。本研究旨在比较翼状胬肉和健康对照组织中 GrB 的表达,并进一步将这种 GrB 表达与肥大细胞联系起来。使用死后翼状胬肉组织和年龄匹配的对照结膜组织,通过免疫荧光和显微镜评估 GrB 的表达。我们发现,与健康对照组相比,翼状胬肉标本中 GrB+细胞的密度明显更高。此外,翼状胬肉标本中的许多 GrB+细胞共同表达了胰蛋白酶,这是一种肥大细胞标志物。这些发现表明结膜肥大细胞分泌的 GrB 在翼状胬肉的发病机制中起作用,并强调 GrB 可能是延迟或阻止翼状胬肉进展的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4b/11354738/cbec1d858d40/ijms-25-08679-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4b/11354738/f9211cd782a5/ijms-25-08679-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4b/11354738/af9733ec42f8/ijms-25-08679-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4b/11354738/319012aa2a1f/ijms-25-08679-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4b/11354738/cbec1d858d40/ijms-25-08679-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4b/11354738/f9211cd782a5/ijms-25-08679-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4b/11354738/af9733ec42f8/ijms-25-08679-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4b/11354738/319012aa2a1f/ijms-25-08679-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed4b/11354738/cbec1d858d40/ijms-25-08679-g004.jpg

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Lab Invest. 2023 Jun;103(6):100123. doi: 10.1016/j.labinv.2023.100123. Epub 2023 Feb 26.
2
Potential role of extracellular granzyme B in wet age-related macular degeneration and fuchs endothelial corneal dystrophy.细胞外颗粒酶B在湿性年龄相关性黄斑变性和富克斯内皮性角膜营养不良中的潜在作用。
Front Pharmacol. 2022 Sep 20;13:980742. doi: 10.3389/fphar.2022.980742. eCollection 2022.
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Matrix Metalloproteinase-14 as an Instigator of Fibrosis in Human Pterygium and Its Pharmacological Intervention.
基质金属蛋白酶-14作为人翼状胬肉纤维化的引发因素及其药物干预
ACS Pharmacol Transl Sci. 2022 Jul 19;5(8):555-561. doi: 10.1021/acsptsci.2c00125. eCollection 2022 Aug 12.
4
The Role of the Stromal Extracellular Matrix in the Development of Pterygium Pathology: An Update.基质细胞外基质在翼状胬肉病理发展中的作用:最新进展
J Clin Med. 2021 Dec 17;10(24):5930. doi: 10.3390/jcm10245930.
5
Granzyme B mediates impaired healing of pressure injuries in aged skin.颗粒酶B介导老年皮肤压力性损伤愈合受损。
NPJ Aging Mech Dis. 2021 Mar 5;7(1):6. doi: 10.1038/s41514-021-00059-6.
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Granzyme B inhibition reduces disease severity in autoimmune blistering diseases.颗粒酶 B 抑制可减轻自身免疫性水疱病的疾病严重程度。
Nat Commun. 2021 Jan 12;12(1):302. doi: 10.1038/s41467-020-20604-3.
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