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.

Investigator‐initiated clinical study of a functional peptide, SR‐0379, for limb ulcers of patients with Werner syndrome as a pilot study

“…We have developed a number of novel peptide drugs to treat skin ulcers over the past 10 years, beginning with a discovery in basic science experiments and extending to clinical trials to evaluate the safety and efficacy for the treatment of severe limb ulcers. 8,13,[15][16][17] In the present study, we evaluated the effect of SR-0379 on limb ulcers in Werner syndrome patients.…”

Tissue-dependent induction of antimicrobial peptide genes after body wall injury in house fly (<i>Musca domestica</i>) larvae

“…AMP, such as polymyxin B and colistin, is clinically used as an antimicrobial agent (47). Interestingly, some AMPs showed biological activities, such as immunomodulation, angiogenesis, and wound healing, against mammalian cells and tissues (48)(49)(50). The usefulness of injuryinducible AMP genes in house fly is limited now, and the further study of the AMP is necessary for the formation of grounds of the practical use.…”

Physician‐initiated first‐in‐human clinical study using a novel angiogenic peptide, AG30/5C, for patients with severe limb ulcers

“…Based on these results, we have already developed the modified AG30/5C peptide, named SR‐0379 . Recently, another anti‐microbial peptide, LL‐37, was similarly evaluated for venous leg ulcers .…”