Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing

Abstract

Cathelicidins play pivotal roles in host defense. The discovery of novel cathelicidins is important research; however, despite the identification of many cathelicidins in vertebrates, few have been reported in amphibians. Here we identified a novel cathelicidin (named cathelicidin-OA1) from the skin of an amphibian species, Odorrana andersonii. Produced by posttranslational processing of a 198-residue prepropeptide, cathelicidin-OA1 presented an amino acid sequence of ‘IGRDPTWSHLAASCLKCIFDDLPKTHN′ and a molecular mass of 3038.5 Da. Functional analysis showed that, unlike other cathelicidins, cathelicidin-OA1 demonstrated no direct microbe-killing, acute toxicity and hemolytic activity, but did exhibit antioxidant activity. Importantly, cathelicidin-OA1 accelerated wound healing against human keratinocytes (HaCaT) and skin fibroblasts (HSF) in both time- and dose-dependent manners. Notably, cathelicidin-OA1 also showed wound-healing promotion in a mouse model with full-thickness skin wounds, accelerating re-epithelialization and granulation tissue formation by enhancing the recruitment of macrophages to the wound site, inducing HaCaT cell proliferation and HSF cell migration. This is the first cathelicidin identified from an amphibian that shows potent wound-healing activity. These results will help in the development of new types of wound-healing agents and in our understanding of the biological functions of cathelicidins.

A frog cathelicidin peptide effectively promotes cutaneous wound healing in mice

“…Tylotoin increased TGF-β1 and IL-6 secretion in a dose-dependent manner in the culture supernatants of RAW264.7 and it had no significant effect on IL-1β, EGF and TNF-α secretion [ 17 ]. Cathelicidin-OA1 promoted the secretion of TNF-α and TGF-β in the human monocyte-like cell line THP-1 [ 18 ], and the authors did not detect the effect of cathelicidin-OA1 on other cytokines and chemokines. Additionally, the human cathelicidin LL-37, which was the best characterized member of the cathelicidin family, has been shown to exhibit wound healing-promoting activities in vitro and in vivo .…”

“…Currently, only two cathelicidins with wound-healing ability have been characterized in amphibians. One is tylotoin, which was isolated from the salamander Tylototriton verrucosus (Caudata: Salamandridae) [ 17 ]; the other is cathelicidin-OA1, which was identified from the Chinese odorous frog Odorrana andersonii (Anura: Ranidae) [ 18 ]. Additionally, two non-cathelicidin peptides (CW49 and AH90) from frog skin secretions and one designed peptide (tiger17) based on frog antimicrobial peptides, also showed wound-healing ability [ 19 – 21 ].…”

Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activation in Microglia and Hippocampal Neurons

“…9A). After 30 minutes of incubation with Ocellatin-K1 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), no significant morphological changes in the cells were found at the concentrations tested (250, 500 and 1000 µg/mL; Fig. 9B-F, respectively).…”

“…molecules, such as peptides, by glands located in the dermis of these animals 4 . Nevertheless, this vulnerability may reappear in the presence of a global biotic threat such as the chytridiomycosis that promoted a huge reduction of Amphibian biodiversity affecting many species of the Leptodactylidae family 5 .…”

“…Ocellatin-K1(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and Ocellatin-K1(1-21) protect hippocampal neurons from oxidative stress induced by LPS-treated-microglial conditioned media. Representative confocal images and quantification of ROS production in hippocampal neurons incubated with conditioned medium from microglia subjected to LPS-induced and 100 μM Ocellatin-K1(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) or Ocellatin-K1(1-21). Images show neurons expressing mVenus (green) and the Hyper Red ROS biosensor (red).…”