26 Chapter 2 Table 1: Summary of recent studies illustrating changes related to ECM in fibrosis and their impacts on cell responses. Category Changes in ECM Cellular Response Reference ECM Crosslinking Pan-inhibition of LO activity Lower rates of TGF-β induced collagen remodeling and ECM stiffness in human primary lung fibroblasts seeded on decellularized cell-derived ECM [11] Increased ECM crosslinking by TG2 Higher rates of proliferation in human primary lung fibroblasts seeded on decellularized IPF cell-derived ECM [29] Knock out of LOXL3 by siRNA Lower rates of fibroblast-tomyofibroblast differentiation in normal human lung fibroblasts [50] Deficiency of LOXL1 Lower expressions of TGF-β, collagen type I and αSMA in TGF-β overexpression mice model of fibrosis at day 35 compared to wild type mice of the same model [51] Stiffness Increased stiffness in 2D polyacrylamide hydrogels Faster migration and higher spread area normal human lung fibroblasts [31] Increased stiffness in 2D collagen type I-coated culture higher rate of activation and higher nuclear volume in murine primary lung fibroblasts [32] Increased stiffness of fibronectin coated polyacrylamide hydrogels Higher αSMA expression in murine lung fibroblasts [33] Increased stiffness of polyacrylamide hydrogels functionalized with solubilized matrix from lungs Higher cell area and higher αSMA expression in human primary microvascular pericytes [26] Increased stiffness in 2D dextranbased hydrogels functionalized with MMP-cut sites Higher myofibroblast differentiation in normal human lung fibroblasts [12] Increased stiffness in 3D dextranbased hydrogels functionalized with MMP-cut sites Lower myofibroblast differentiation in normal human lung fibroblasts [12] Topography Thicker collagen fibers in 3D collagen type I hydrogels Higher myofibroblast differentiation in human adipose derived stromal cells [39] Increased alignment of collagen type I -methacrylated gelatin hydrogel networks Increased migration speed in human primary lung fibroblasts in 2D [40] Increasing fiber density in 3D dextran-based hydrogels functionalized with MMP-cut sites Higher myofibroblast differentiation, cell spread area, YAP translocation and proliferation rate in normal human lung fibroblasts [12] LO: Lysyl oxidase, ECM: Extracellular matrix, TG: Transglutaminase, LOXL: Lysyl oxidase-like, TGF-β: Transforming growth factor β, αSMA: α Smooth muscle actin, MMP: Matrix metalloproteinase, YAP: Yes-associated protein
RkJQdWJsaXNoZXIy MTk4NDMw