Identification of peptide inhibitors of transforming growth factor beta 1 using a phage-displayed peptide library

Pathologies such as liver fibrosis and scleroderma are characterized by harmful levels of transforming growth factor beta 1 (TGFβ1). These levels could be neutralized if inhibitors of this cytokine were available. With this aim we searched for peptides with binding affinity for TGFβ1 using a phage-displayed random 15-mer peptide library. Some peptides thus identified blocked activity of TGFβ1 in vitro, as measured by their capacity to restore growth of Mv-1-Lu cells in presence of added TGFβ1. Also, they inhibited TGFβ1-dependent expression of collagen type I mRNA in liver of mice orally insulted with CCl4. Intraperitoneal administration of 50 μg of peptide P17 (the most active 15-mer peptide, also referred to as P17(1–15)) inhibited expression of collagen type I mRNA by almost 100%. Interestingly, titration experiments showed that P17(1–12) (a peptide encompassing the first 12 amino acids of P17) was approximately four times more active than P17. These results suggest that both peptides, as well as others reported here, may be of therapeutic interest in processes requiring control of undesired high levels of TGFβ1.