Uristatin Anti-inflammatory Cellular Signaling

The Inter-α-Trypsin Inhibitor Family: Versatile Molecules in Biology and Pathology

“…Bikunin is also recognized to exhibit a range of cell signaling functions mediated at the cell surface via interactions with cartilage link protein (HAPLN1), an HA binding protein, and an as-yet-unidentified protein named the bikunin receptor. 5,116 Notably, bikunin inhibits cell invasion via inhibition of transforming growth factor (TGF)-β1 expression, which in turn inhibits selected mitogen-activated protein (MAP) kinase signaling pathways including Src-, MEK-, and ERK-dependent urokinase-type plasminogen activator (uPA) and uPA receptor expression. 117–121 Bikunin can reduce cell proliferation via disrupting the heterodimerization of CD44 with growth factors, resulting in the suppression of receptor-mediated MAP kinase signaling.…”

“…More recent studies on IαI have revealed its localization in many tissues with diverse roles in cell regulation and matrix integrity (Table 1) in both health and disease. 5,6 Although the liver is recognized as the main source of IαI, 7–12 many other tissues synthesize IαI family components, including the kidney, 13 reproductive tissues, 14 lung, 15 connective tissues, 16–18 and central nervous system 19,20 (Table 2). Much research focus has been placed on the roles of IαI in pathology, and notably in inflammation, whereas its physiological roles, apart from those in ovulation, are less explored.…”