No 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.

AA and CPG are co-inventors on patents assigned to Health Innovation Ventures (PCT/WO 2014031012 A1). AH, JT, and LD have shares in the company Convert Pharmaceuticals, and LD has a non-issue, non-licensed patent on LSRT (N2024889). JBS and AVP have served as scientific consultants to Convert Pharmaceuticals. AH, ST, and SD have been prior employees of Convert Pharmaceuticals. PL reports -within and outside the submitted work -grants or sponsored research agreements from Varian Medical, Oncoradiomics, ptTheragnostic/DNAmito, Convert Pharmaceuticals, and Health Innovation Ventures. He received an advisor/presenter fee and/or reimbursements of travel costs/external grant writing fee and/or kind manpower contribution from Oncoradiomics, BHV, Merck, Varian, Elekta, ptTheragnostic, and Convert Pharmaceuticals. PL has shares in the company Oncoradiomics SA, Convert Pharmamaceuticals, LivingMed Biotech, and Comunicare Solutions, and is co-inventor of two issues patents with royalties on radiomics (PCT/NL2014/050248, PCT/NL2014/050728) licensed to Oncoradiomics, one issue patent on mtDNA (PCT/EP2014/059089) licensed to ptTheragnostic/DNAmito, three non-patented inventions (software) licensed to ptTheragnostic/DNAmito and Oncoradiomics and Health Innovation Ventures, and three non-issues, non-licensed patents on Deep Learning-Radiomics and LSRT (N2024482, N2024889, N2024889).