Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.

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 t...

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Main Authors: Hideki Tomioka, Hironori Nakagami, Akiko Tenma, Yoshimi Saito, Toshihiro Kaga, Toshihide Kanamori, Nao Tamura, Kazunori Tomono, Yasufumi Kaneda, Ryuichi Morishita
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092597&type=printable
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author Hideki Tomioka
Hironori Nakagami
Akiko Tenma
Yoshimi Saito
Toshihiro Kaga
Toshihide Kanamori
Nao Tamura
Kazunori Tomono
Yasufumi Kaneda
Ryuichi Morishita
author_facet Hideki Tomioka
Hironori Nakagami
Akiko Tenma
Yoshimi Saito
Toshihiro Kaga
Toshihide Kanamori
Nao Tamura
Kazunori Tomono
Yasufumi Kaneda
Ryuichi Morishita
author_sort Hideki Tomioka
collection DOAJ
description 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.
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spelling doaj-art-d5754996943347d7afc9ee5bc2b88ae72025-08-20T03:01:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9259710.1371/journal.pone.0092597Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.Hideki TomiokaHironori NakagamiAkiko TenmaYoshimi SaitoToshihiro KagaToshihide KanamoriNao TamuraKazunori TomonoYasufumi KanedaRyuichi MorishitaWe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092597&type=printable
spellingShingle Hideki Tomioka
Hironori Nakagami
Akiko Tenma
Yoshimi Saito
Toshihiro Kaga
Toshihide Kanamori
Nao Tamura
Kazunori Tomono
Yasufumi Kaneda
Ryuichi Morishita
Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.
PLoS ONE
title Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.
title_full Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.
title_fullStr Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.
title_full_unstemmed Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.
title_short Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.
title_sort novel anti microbial peptide sr 0379 accelerates wound healing via the pi3 kinase akt mtor pathway
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0092597&type=printable
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