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Abstract #105839 Published in IGR 23-3
Fibrotic Response of Human Trabecular Meshwork Cells to Transforming Growth Factor-Beta 3 and Autotaxin in Aqueous Humor
Liu M; Honjo M; Yamagishi R; Igarashi N; Nakamura N; Kurano M; Yatomi Y; Igarashi K; Aihara MBiomolecules 2022; 12:
This study examines the potential role of transforming growth factor-beta 3 (TGF-β3) on the fibrotic response of cultured human trabecular meshwork (HTM) cells. The relationships and trans-signaling interactions between TGF-β3 and autotaxin (ATX) in HTM cells were also examined. The levels of TGF-β and ATX in the aqueous humor (AH) of patients were measured by an immunoenzymetric assay. The TGF-β3-induced expression of the fibrogenic markers, fibronectin, collagen type I alpha 1 chain, and alpha-smooth muscle actin, and ATX were examined by quantitative real-time PCR, Western blotting, and immunocytochemistry, and the trans-signaling regulatory effect of TGF-β3 on ATX expression was also evaluated. In HTM cells, the significant upregulation of ATX was induced by TGF-β3 at a concentration of 0.1 ng/mL, corresponding to the physiological concentration in the AH of patients with exfoliative glaucoma (XFG). However, higher concentrations of TGF-β3 significantly suppressed ATX expression. TGF-β3 regulated ATX transcription and signaling in HTM cells, inducing the upregulation of fibrogenic proteins in a dose-dependent manner. Trans-signaling of TGF-β3 regulated ATX transcription, protein expression, and signaling, and was thereby suggested to induce fibrosis of the trabecular meshwork. Modulation of trans-signaling between TGF-β3 and ATX may be key to elucidate the pathology of XFG, and for the development of novel treatment modalities.
Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
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