NFATc1 Regulation of Dexamethasone-Induced TGFB2 Expression Is Cell Cycle Dependent in Trabecular Meshwork Cells

卷:12

Article

关键词: GROWTH-FACTOR BETA-2;    AQUEOUS-HUMOR;    INTRAOCULAR-PRESSURE;    EXTRACELLULAR-MATRIX;    CONTACT INHIBITION;    RETINOIC ACID;    IN-VITRO;    TGF-BETA-2;    CULTURE;    CALCINEURIN;   

DOI  :  10.3390/cells12030504

来源: SCIE

【 摘 要 】

Although elevated TGF beta 2 levels appear to be a causative factor in glaucoma pathogenesis, little is known about how TGF beta 2 expression is regulated in the trabecular meshwork (TM). Here, we investigated if activation of the cytokine regulator NFATc1 controlled transcription of TGF beta 2 in human TM cells by using dexamethasone (DEX) to induce NFATc1 activity. The study used both proliferating and cell cycle arrested quiescent cells. Cell cycle arrest was achieved by either cell-cell contact inhibition or serum starvation. beta-catenin staining and p21 and Ki-67 nuclear labeling were used to verify the formation of cell-cell contacts and activity of the cell cycle. NFATc1 inhibitors cyclosporine A (CsA) or 11R-VIVIT were used to determine the role of NFATc1. mRNA levels were determined by RT-qPCR. DEX increased TGF beta 2 mRNA expression by 3.5-fold in proliferating cells but not in quiescent cells or serum-starved cells, and both CsA and 11R-VIVIT inhibited this increase. In contrast, the expression of other DEX/NFATc1-induced mRNAs (myocilin and beta 3 integrin) occurred regardless of the proliferative state of the cells. These studies show that NAFTc1 regulates TGF beta 2 transcription in TM cells and reveals a previously unknown connection between the TM cell cycle and modulation of gene expression by NFATc1 and/or DEX in TM cells.