Recombinant Mouse TSG-6 Protein, CF

TSG-6 (TNF-stimulated gene 6; also named TNFIP6) is a secreted, 35 - 39 kDa group A member of the LINK-Module superfamily of proteins (1 - 4). Mouse TSG-6 is synthesized as a 275 amino acid (aa) precursor. It contains a 17 aa signal sequence and a 258 aa mature region (5, 6). The mature region has an N-terminal link module (aa 36 - 129) and a C-terminal CUB (C1s/C1r; urchin embryonic growth factor; BMP1) domain (aa 135 - 246). Link modules bind hyaluronan (HA) and participate in extracellular matrix (ECM) assembly (7). Mature mouse TSG-6 shares 97%, 94% and 94% aa identity with rat, human and canine TSG-6, respectively. Cells reported to express TGF-6 include activated fibroblasts, synoviocytes, chondrocytes, neutrophils, proximal tubular epithelium, bronchial epithelium, endothelium, and visceral plus vascular smooth muscle (2, 8). TSG-6 has multiple functions, many of which involve the ECM. It is suggested to stabilize HA-rich ECM. It does so by serving as an intermediary, or as a link between the individual subunits of the extracellular decameric pentraxin 3 and the surrounding hyaluronan matrix (9). It also provides structure and organization to hyaluronan. This is accomplished by a TSG-6 mediated transfer of an 80 - 85 kDa protein subunit from I alphaI (inter-alpha -inhibitor) to HA. I alphaI is a four-component, 225 kDa serine protease inhibitor. It contains a protease inhibitor subunit (bikunin), two independent, accompaning protein chains (HC1 and HC2), and a short chondroitin sulfate linking moiety. TSG-6 is a catalyst for the removal and transient binding of either HC chain. Each chain is subsequently transferred and covalently-linked to the surrounding HA. This provides substance and reinforcement to the ECM (1, 2, 10, 11, 12). This disassembly of I alphaI also leads to free bikunin, which in the “free” state becomes a potent inhibitor of serine proteases (8).