Recombinant Human TSG-6 Protein, CF

TSG-6 (TNF-stimulated gene 6; also TNFIP6) is a secreted, 35-39 kDa group A member of the LINK‑Module superfamily of proteins (1 - 4). Human TSG‑6 is synthesized as a 277 amino acid (aa) precursor. It contains a 17 aa signal sequence and a 260 aa mature region (5, 6). The mature region shows an N-terminal LINK module (aa 36-129) and a C-terminal CUB (C1s/C1r; urchin embryonic growth factor; BMP1) domain (aa 135-247). Link modules are alpha -helical, beta -sheet structures that bind hyaluronan (HA) and participate in extracellular matrix (ECM) assembly (7). Mature human TSG-6 shares 94% aa identity with both mouse and canine TSG-6. Cells reported to express TSG-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 link, between the individual subunits of 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 HC subunit from I alpha I (inter-alpha -inhibitor) to HA. I alpha I 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 cation‑dependent catalyst for the removal, transfer, and subsequent covalent linkage of HC 1/2 to surrounding HA. This provides substance and reinforcement to the ECM (1, 2, 10, 11, 12). The disassembly of I alpha I also leads to free bikunin, which in the “free” state becomes a potent inhibitor of serine proteases (8).