title: Identification of peptide inhibitors of transforming growth factor beta 1 using a phage-displayed peptide library.
abstract: Pathologies such as liver fibrosis and scleroderma are characterized by harmful levels of transforming growth factor beta 1 (TGFbeta1). These levels could be neutralized if inhibitors of this cytokine were available. With this aim we searched for peptides with binding affinity for TGFbeta1 using a phage-displayed random 15-mer peptide library. Some peptides thus identified blocked activity of TGFbeta1 in vitro, as measured by their capacity to restore growth of Mv-1-Lu cells in presence of added TGFbeta1. Also, they inhibited TGFbeta1-dependent expression of collagen type I mRNA in liver of mice orally insulted with CCl(4). Intraperitoneal administration of 50 microg 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 TGFbeta1.
authors.affiliation: Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pío XII, 55-31008-Pamplona, Spain. jdotor@unav.es
authors.forename: Javier
authors.initials: J
authors.lastname: Dotor
authors.forename: Ana B
authors.initials: AB
authors.lastname: López-Vázquez
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lasarte
authors.forename: Pablo
authors.initials: P
authors.lastname: Sarobe
authors.forename: Marta
authors.initials: M
authors.lastname: García-Granero
authors.forename: José I
authors.initials: JI
authors.lastname: Riezu-Boj
authors.forename: Alfonso
authors.initials: A
authors.lastname: Martínez
authors.forename: Esperanza
authors.initials: E
authors.lastname: Feijoó
authors.forename: Jacinto
authors.initials: J
authors.lastname: López-Sagaseta
authors.forename: José
authors.initials: J
authors.lastname: Hermida
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.forename: Francisco
authors.initials: F
authors.lastname: Borrás-Cuesta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008099:Liver / Q000293:injuries / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein; D020349:Surface Plasmon Resonance; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*