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IgG4 相关眼病患者泪腺中肥大细胞衍生的糜酶的激活。

Activation of Mast-Cell-Derived Chymase in the Lacrimal Glands of Patients with IgG4-Related Ophthalmic Disease.

机构信息

Department of Ophthalmology, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan.

Department of Innovative Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Japan.

出版信息

Int J Mol Sci. 2022 Feb 25;23(5):2556. doi: 10.3390/ijms23052556.

DOI:10.3390/ijms23052556
PMID:35269701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8910072/
Abstract

The purpose of this present study was to investigate the distribution and expression of chymase in the lacrimal glands (LGs) of patients afflicted with IgG4-related ophthalmic disease (IgG4-ROD). LGs from patients with severe canalicular obstruction were considered the control group. Toluidine blue staining confirmed a significant increase in the number of mast cells in the LGs obtained from the IgG4-ROD patients. In addition, immunostaining of serial sections from the LGs showed a significant increase in the number of chymase-positive cells and tryptase-positive cells in the IgG4-ROD LGs compared to the normal control LGs. The mRNA expression of chymase, tryptase, TGF-β1, and collagen-I tended to increase in the IgG4-ROD LGs. Immunostaining of vimentin and α-smooth muscle actin (α-SMA) showed that myofibroblasts were the main cellular components in severely fibrotic regions of LGs in patients with IgG4-ROD. Linear regression analyses on the number of mast cells, chymase-positive cells, and tryptase-positive cells revealed significant positive correlations between those respective cells. Our findings suggest that chymase may play a role in the fibrotic disorder of IgG4-ROD LGs through the regulation of TGF-β1 activation and collagen-I deposition, and that it may be a therapeutic target for patients afflicted with IgG4-ROD.

摘要

本研究旨在探讨 IgG4 相关眼病（IgG4-ROD）患者泪腺（LGs）中糜酶的分布和表达。将严重泪道阻塞患者的 LG 作为对照组。甲苯胺蓝染色证实，IgG4-ROD 患者 LG 中的肥大细胞数量显著增加。此外，LG 连续切片的免疫染色显示，与正常对照组 LG 相比，IgG4-ROD LG 中糜酶阳性细胞和类胰蛋白酶阳性细胞的数量显著增加。糜酶、类胰蛋白酶、TGF-β1 和胶原-I 的 mRNA 表达在 IgG4-ROD LG 中趋于增加。波形蛋白和α-平滑肌肌动蛋白（α-SMA）的免疫染色显示，肌成纤维细胞是 IgG4-ROD 患者 LG 严重纤维化区域的主要细胞成分。对肥大细胞、糜酶阳性细胞和类胰蛋白酶阳性细胞数量的线性回归分析显示，这些细胞之间存在显著的正相关关系。我们的研究结果表明，糜酶可能通过调节 TGF-β1 的激活和胶原-I 的沉积，在 IgG4-ROD LG 的纤维化紊乱中发挥作用，并且可能是 IgG4-ROD 患者的治疗靶点。

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