chir-99021 and Fibrosis

This study investigated the effect of glycogen synthase kinase-3β (GSK-3β) inhibition on the fibrosis of human Tenon's fibroblasts (HTFs) induced by transforming growth factor-β (TGF-β).. Quantitative real-time PCR and Western blot analyses were performed to determine the expression levels of molecules associated with the fibrosis of HTFs by TGF-β (fibronectin, collagen Iα, and α-smooth muscle actin) and GSK-3β. The levels of phosphorylated Smad2 and Smad3 were also analyzed in the presence of the GSK-3β inhibitor CHIR 99021. The wound healing assay was performed to determine the effect of CHIR 99021 on the migration of HTFs. All experiments were conducted using primary cultured HTFs or human tenon tissues obtained from normal subjects and patients with glaucoma.. Treatment with TGF-β resulted in an increase in the levels of molecules associated with the fibrosis of HTFs. The expression levels of these molecules were higher in the tenon tissues obtained from patients with glaucoma than those from normal subjects. When the HTFs were treated with TGF-β, a significant increase in the active form of GSK-3β (Y216) was observed. A significant decrease in the active form of GSK-3β and molecules associated with fibrosis by TGF-β was noted in HTFs treated with CHIR 99021. CHIR 99021 treatment reduced the phosphorylated Smad2/Smad2 and phosphorylated Smad3/Smad3 ratios in HTFs and attenuated HTF migration.. Our results demonstrated the effect of GSK-3β inhibition on the regulation of TGF-β-mediated fibrosis of HTFs, suggesting GSK-3β to be a potential target for maintaining bleb function after glaucoma filtration surgery.

Topics: Actins; Blotting, Western; Cells, Cultured; Collagen Type I, alpha 1 Chain; Enzyme Inhibitors; Fibroblasts; Fibronectins; Fibrosis; Glycogen Synthase Kinase 3 beta; Humans; Pyridines; Pyrimidines; Real-Time Polymerase Chain Reaction; Tenon Capsule; Transforming Growth Factor beta

Healthy aging results in cardiac structural and electrical remodeling that increases susceptibility to cardiovascular diseases. Relaxin, an insulin-like hormone, suppresses atrial fibrillation, inflammation and fibrosis in aged rats but the mechanisms-of-action are unknown. Here we show that relaxin treatment of aged rats reverses pathological electrical remodeling (increasing Nav1.5 expression and localization of Connexin43 to intercalated disks) by activating canonical Wnt signaling. In isolated adult ventricular myocytes, relaxin upregulated Nav1.5 (EC

Topics: Adult; Age Factors; Aged; Animals; Atrial Fibrillation; Cells, Cultured; Fibroblasts; Fibrosis; Glycogen Synthase Kinase 3 beta; Healthy Aging; Humans; Isolated Heart Preparation; Male; Myocardium; Myocytes, Cardiac; Primary Cell Culture; Pyridines; Pyrimidines; Rats; Relaxin; Ventricular Remodeling; Wnt Signaling Pathway; Wnt1 Protein