Recombinant Mouse Follistatin-like 1 Protein, CF

Follistatin-like 1 (FSTL1 or FSL1), also known as FRP (follistatin-related protein), Flik (follistatin-like), and TSC-36 (TGF-beta 1-stimulated clone 36), is a secreted 45‑55 kDa extracellular glycoprotein belonging to the BM-40/SPARC/Osteonectin family (1-3). The mouse FSTL1 cDNA encodes 306 amino acids (aa), including an 18 aa signal sequence, a cysteine-rich Follistatin (EGF- and kazal-like) domain, two apparently nonfunctional EF-hand calcium-binding motifs, and a von Willebrand Factor C homology domain (1, 3). Mature mouse FSTL1 shares 94%, 96%, 94%, 93% and 93% aa identity with human, rat, equine, bovine and canine FSTL1, respectively. FSTL1 was first identified as a TGF-beta -induced protein from a mouse osteoblast cell line (4). It is ubiquitously expressed in early mouse development, but is mainly mesenchymal later in development (5). In vitro, FSTL1 interacts directly with BMP-4, while in vivo, it regulates BMP-4 signaling during normal lung development, as demonstrated by lethal respiratory failure in mice deleted for FSTL1 (6). In humans, FSTL1 is a common rheumatoid arthritis autoantigen (2). It is reported to be either proinflammatory due to promoting inflammatory cytokine secretion, or to prevent autoimmune arthritis by inhibiting matrix metalloproteinase (MMP) and prostaglandin expression (7-10). In muscle and heart, it appears to be protective and promotes endothelial cell functions such as revascularization after ischemia, probably due to promoting expression and activation of the protein kinase AKT1 (11, 12). Cardiac and circulating FSTL1 is generally increased in conditions such as heart failure and acute coronary syndrome (12-14). FSTL1 also appears to be a tumor suppressor, showing down‑regulated expression in many human cancers (4, 15, 16). In vitro, it slows proliferation and MMP-dependent migration, and increases FAS-dependent apoptosis of tumor cell lines (15).