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Abstract:Vitamin A derivative, all-trans-retinoic acid (ATRA), is known to be a potent regulator of the growth and differentiation of various types of cells. In the present study, the unidentified effects of ATRA on superficial and vertical spreading conjunctival scarring were examined. The study involved the use of two-dimensional (2D) and three-dimensional (3D) cultures of human conjunctival fibroblast (HconF) cells in the presence or absence of TGF-β2. The effects of ATRA (1 μM) on superficial or vertical spreading conjunctival scarring were evaluated by the barrier function by trans-endothelial electrical resistance (TEER) and FITC dextran permeability measurements and real-time metabolic analysis, as well as the physical properties, namely, the size and stiffness, of 3D spheroids, respectively. In addition, the expressions of several related molecules, including extracellular matrix (ECM) molecules, ECM modulators including a tissue inhibitor of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs), and ER stress-related factors, were examined. ATRA significantly induced (1) an increase in TEER values and a decrease in FITC dextran permeability, respectively, in the 2D monolayers, and (2) relatively and substantially increased the size and stiffness, respectively, of the 3D spheroids. These ATRA-induced effects were further enhanced in the TGF-β2-treated cells, whereas the TGF-β2-induced enhancement in glycolytic capacity was canceled by the presence of ATRA. Consistent with these physical and morphological effects, the mRNA expressions of several molecules were significantly but differently induced between 2D and 3D cultures by ATRA, although the presence of TGF-β2 did not substantially affect these gene expression levels. The findings reported in this study indicate that ATRA may exacerbate both superficial and vertical conjunctival fibrosis spreading independently of TGF-β2-induced changes.Keywords: three-dimensional spheroid cultures; human conjunctival fibroblast (HconF); all-trans-retinoic acid (ATRA); TGF-β2
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Chan, Sander and Bauer, Steffen and Betsill, Michele M. and Biermann, Frank and Boran, Idil and Bridgewater, Peter and Bulkeley, Harriet and Bustamente, Mercedes M.C. and Deprez, Alexandra and Dodds, Felix and Hoffmann, Michael and Hornidge, Anna-Katharina and Hughes, Alice and Imbach, Pablo and Ivanova, Maria and Köberle, Alexandre and Kok, Marcel T.J. and Lwasa, Shuaib and Morrison, Tiffany and Pörtner, Hans -O. and Sari, Agus P. and VanDeveer, Stacy D. and Vollmer, Derek and Widerberg, Oscar and Pettorelli, Nathalie (2022) 'The Global Biodiversity Framework Needs a Robust Action Agenda.', Nature Ecology & Evolution .
Müller, Juliane and Romero, Oscar and Cowan, Ellen A. and McClymont, Erin L. and Forwick, Matthias and Asahi, Hirofumi and März, Christian and Moy, Christopher M. and Suto, Itsuki and Mix, Alan and Stoner, Joseph (2018) 'Cordilleran ice-sheet growth fueled primary productivity in the Gulf of Alaska, northeast Pacific Ocean.', Geology., 46 (4). pp. 307-310. 041b061a72