Activation of Mast-Cell-Derived Chymase in the Lacrimal Glands of Patients with IgG4-Related Ophthalmic Disease
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES(2022)
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-beta 1, and collagen-I tended to increase in the IgG4-ROD LGs. Immunostaining of vimentin and alpha-smooth muscle actin (alpha-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-beta 1 activation and collagen-I deposition, and that it may be a therapeutic target for patients afflicted with IgG4-ROD.
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Key words
chymase,mast cells (MCs),IgG4-related ophthalmic disease (IgG4-ROD),lacrimal glands (LGs),transforming growth factor-beta 1 (TGF-beta 1)
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