PMID- 17804251 OWN - NLM STAT- MEDLINE DCOM- 20080118 LR - 20071010 IS - 1043-4666 (Print) IS - 1043-4666 (Linking) VI - 39 IP - 2 DP - 2007 Aug TI - Identification of peptide inhibitors of transforming growth factor beta 1 using a phage-displayed peptide library. PG - 106-15 AB - 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. FAU - Dotor, Javier AU - Dotor J AD - Division of Hepatology and Gene Therapy, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pio XII, 55-31008-Pamplona, Spain. jdotor@unav.es FAU - Lopez-Vazquez, Ana B AU - Lopez-Vazquez AB FAU - Lasarte, Juan J AU - Lasarte JJ FAU - Sarobe, Pablo AU - Sarobe P FAU - Garcia-Granero, Marta AU - Garcia-Granero M FAU - Riezu-Boj, Jose I AU - Riezu-Boj JI FAU - Martinez, Alfonso AU - Martinez A FAU - Feijoo, Esperanza AU - Feijoo E FAU - Lopez-Sagaseta, Jacinto AU - Lopez-Sagaseta J FAU - Hermida, Jose AU - Hermida J FAU - Prieto, Jesus AU - Prieto J FAU - Borras-Cuesta, Francisco AU - Borras-Cuesta F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070904 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Peptide Library) RN - 0 (Peptides) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Amino Acid Sequence MH - Animals MH - Cells, Cultured MH - Disease Models, Animal MH - Liver/injuries/pathology MH - Mice MH - Molecular Sequence Data MH - *Peptide Library MH - Peptides/*pharmacology MH - Protein Binding MH - Rats MH - Rats, Wistar MH - Sequence Analysis, DNA MH - Sequence Analysis, Protein MH - Surface Plasmon Resonance MH - Transforming Growth Factor beta1/*antagonists & inhibitors EDAT- 2007/09/07 09:00 MHDA- 2008/01/19 09:00 CRDT- 2007/09/07 09:00 PHST- 2006/11/28 00:00 [received] PHST- 2007/06/08 00:00 [revised] PHST- 2007/06/18 00:00 [accepted] PHST- 2007/09/07 09:00 [pubmed] PHST- 2008/01/19 09:00 [medline] PHST- 2007/09/07 09:00 [entrez] AID - S1043-4666(07)00161-5 [pii] AID - 10.1016/j.cyto.2007.06.004 [doi] PST - ppublish SO - Cytokine. 2007 Aug;39(2):106-15. doi: 10.1016/j.cyto.2007.06.004. Epub 2007 Sep 4.