Fibrotic Response of Human Trabecular Meshwork Cells to Transforming Growth Factor-Beta 3 and Autotaxin in Aqueous Humor

Abstract

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.

Effects of Bone Marrow Sparing and TGF-β3 Treatment in Total Body Irradiation of C57BL/6J Mice

“…The effect of TGF-β3 on in vitro α-SMA expression, however, appears to vary depending on the model system. TGF-β3 treatment increased the expression of α-SMA mRNA or protein in cultured human trabecular meshwork cells, urinary tract stroma-derived fibroblasts, human uterine fibroid smooth muscle cells, and 3D cultured human corneal fibroblasts (although to a lesser degree than TGF-β1) [73][74][75][76]. In contrast, TGF-β3 treatment in concentrations of 1-100 ng/mL did not increase α-SMA protein content in bovine keratocyte or wounded corneal organ cultures, although TGF-β1 did [77].…”

Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-β/Smad signaling pathway

“…TGF-β3 is a member of multifunctional peptide superfamily, regulates cell growth and differentiation, and exerts a special role in tissue fibrosis ( Liu et al, 2022b ). For example, Liu et al reported that Vgll3 could positively regulate the expression of the key pro-fibrotic factor TGF-β3 and the downstream factor smad2/4.…”