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 (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.
Dotor
Javier
J
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
López-Vázquez
Ana B
AB
Lasarte
Juan J
JJ
Sarobe
Pablo
P
García-Granero
Marta
M
Riezu-Boj
José I
JI
Martínez
Alfonso
A
Feijoó
Esperanza
E
López-Sagaseta
Jacinto
J
Hermida
José
J
Prieto
Jesús
J
Borrás-Cuesta
Francisco
F
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*