Recombinant Human Follistatin-like 1 Protein, CF

Follistatin‑like 1 (FSL1 or FSTL1), 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 human FSL‑1 cDNA encodes 308 amino acids (aa), including a 20 aa signal sequence, a cysteine‑rich Follistatin (EGF- and kazal‑like) domain, two apparently non‑functional EF‑hand calcium‑binding motifs, and a von Willebrand Factor C homology domain (1, 3). Mature human FSL1 shares 94%, 95%, 98% and 99% aa identity with mouse, rat, bovine and equine FSL1, respectively. FSL1 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, FSL1 is a common rheumatoid arthritis auto‑antigen (2). It is reported to be either pro‑inflammatory 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 FSL1 is generally increased in conditions such as heart failure and acute coronary syndrome (12‑14). FSL1 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).