Abstract
How β-catenin/COX-2 contribute to inflammation-induced fibroblasts migration remains poorly understood. Therefore, in this study, lipopolysaccharide (LPS) was used as a stimulus to accelerate the migration of NIH3T3 cells, which mimicked the tissue repair process. LPS treatment increased the cell migration in concentration-and time-dependent manner. And NS398, a COX-2 inhibitor, inhibited LPS-induced NIH3T3 cells migration. DKK-1, an antagonist of the Wnt/β-catenin signaling, also inhibited that migration. However, TWS119, an inducer of β-catenin via GSK-3β, increased the cell migration. LPS or TWS119 treatment increased COX-2, β-catenin, TGF-β1, and HMGB-1 expressions, and that could be attenuated by NS398 or DKK-1 addition. LPS induced the PGE2 production, and PGE2 increased the expression and nuclear translocation of β-catenin, while EP2 blocker, AH6809, alleviated those effects. TWS119 increased the luciferase activity in the COX-2 promoter. In conclusion, LPS stimulated the NIH3T3 fibroblasts migration through a positive feedback between β-catenin and COX-2, in which PGE2, EP2, TGF-β1, and HMGB-1 played as signal molecules.
Highlights
Fibroblasts comprise the most abundant cell type in connective tissues and are central players in organ homeostasis
Compared with the control group, LPS treatment increased both COX-2 and β-catenin expressions (867 ± 37% of the control for COX-2, P < 0.001; 153 ± 1% of the control for β-catenin, P < 0.001). These results suggested that the activation of fibroblast migration by LPS was associated with increases of COX-2 and β-catenin expressions in fibroblasts
Wound healing assays are often studied as a model system for in vivo wound repair, where fibroblasts play an important role in forming the granulation tissue
Summary
Fibroblasts comprise the most abundant cell type in connective tissues and are central players in organ homeostasis. Their main function is to maintain the structural integrity of connective tissue by secreting collagen and fibronectin, which are principal components of the extracellular matrix. Inflammation is part of the complex biological response of body tissues to harmful stimuli. One of the most important function of inflammation is to initiate tissue repair (Pandolfi et al, 2016; Eming et al, 2017). Cyclooxygenase-2 (COX-2) is a key molecule functioning as an early response to pro-inflammatory mediators and stimuli (Rajakariar et al, 2006). Β-Catenin is another molecule playing important roles in inflammation The COX-2 is rapidly induced, and its activity accounts for the large amounts of prostaglandins seen in inflammation. β-Catenin is another molecule playing important roles in inflammation
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