title: Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.
abstract: We developed a novel cationic antimicrobial peptide, AG30/5C, which demonstrates angiogenic properties similar to those of LL-37 or PR39. However, improvement of its stability and cost efficacy are required for clinical application. Therefore, we examined the metabolites of AG30/5C, which provided the further optimized compound, SR-0379. SR-0379 enhanced the proliferation of human dermal fibroblast cells (NHDFs) via the PI3 kinase-Akt-mTOR pathway through integrin-mediated interactions. Furthermore SR-0379 promoted the tube formation of human umbilical vein endothelial cells (HUVECs) in co-culture with NHDFs. This compound also displays antimicrobial activities against a number of bacteria, including drug-resistant microbes and fungi. We evaluated the effect of SR-0379 in two different would-healing models in rats, the full-thickness defects under a diabetic condition and an acutely infected wound with full-thickness defects and inoculation with Staphylococcus aureus. Treatment with SR-0379 significantly accelerated wound healing when compared to fibroblast growth factor 2 (FGF2). The beneficial effects of SR-0379 on wound healing can be explained by enhanced angiogenesis, granulation tissue formation, proliferation of endothelial cells and fibroblasts and antimicrobial activity. These results indicate that SR-0379 may have the potential for drug development in wound repair, even under especially critical colonization conditions.
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan; AnGesMG, Inc., 7-7-15 Saito Bio-Incubator, Ibaraki, Osaka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tomioka
authors.affiliation: Division of Vascular Medicine and Epigenetics, Osaka University United Graduate School of Child Development, 2-1 Yamada-oka, Suita, Osaka, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.affiliation: AnGesMG, Inc., 7-7-15 Saito Bio-Incubator, Ibaraki, Osaka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tenma
authors.affiliation: AnGesMG, Inc., 7-7-15 Saito Bio-Incubator, Ibaraki, Osaka, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Saito
authors.affiliation: AnGesMG, Inc., 7-7-15 Saito Bio-Incubator, Ibaraki, Osaka, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kaga
authors.affiliation: AnGesMG, Inc., 7-7-15 Saito Bio-Incubator, Ibaraki, Osaka, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kanamori
authors.affiliation: AnGesMG, Inc., 7-7-15 Saito Bio-Incubator, Ibaraki, Osaka, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Tamura
authors.affiliation: Division of Infection Control and Prevention, Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tomono
authors.affiliation: Division of Gene Therapy Science, Osaka University Graduate School of Medicine, School of Child Development, 2-1 Yamada-oka, Suita, Osaka, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.affiliation: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008297:Male; D055432:Metabolomics; D008826:Microbial Sensitivity Tests; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C576452:AG30 peptide; D023181:Antimicrobial Cationic Peptides; C000603584:SR-0379; D016222:Fibroblast Growth Factor 2; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases