Exploring the in vivo wound healing effects of a recombinant hemolin from the caterpillar Lonomia obliqua

Abstract

BackgroundHemolin proteins are cell adhesion molecules from lepidopterans involved in a wide range of cell interactions concerning their adhesion properties. However, hemolin’s roles in cell proliferation and wound healing are not fully elucidated. It has been recently reported that rLosac, a recombinant hemolin from the caterpillar Lonomia obliqua, presents antiapoptotic activity and is capable of improving in vitro wound healing. Therefore, this study aimed to explore rLosac’s in vivo effects using a skin wound healing model in rats.MethodsCircular full-thickness wounds in the rat dorsum skin were treated either with rLosac, or with saline (control), allowing healing by keeping the wounds occluded and moist. During the wound healing, the following tissue regeneration parameters were evaluated: wound closure and collagen content. Furthermore, tissue sections were subjected to histological and immunohistochemical analyses.ResultsThe rLosac treatment has demonstrated its capacity to improve wound healing, as reflected in findings of a larger number of activated fibroblasts, proliferation of epithelial cells, increase of collagen type 1, and decrease of inflammatory infiltrate.ConclusionThe findings have indicated the rLosac protein as a very promising molecule for the development of new wound-healing formulations.

Losac and Lopap Recombinant Proteins from Lonomia obliqua Bristles Positively Modulate the Myoblast Proliferation Process

“…To the best of our knowledge, this is the first report that rLosac and rLopap have the ability to stimulate a key process of skeletal muscle regeneration. The stimulatory effect of rLosac on myoblast proliferation is in line with previous reports that this protein promotes proliferation of human endothelial cells ( Bettencourt et al, 1997 ; Bettencourt et al, 1999 ; Alvarez Flores et al, 2006 ; Alvarez-Flores et al, 2011 ; Bosch et al, 2016 ; Sato et al, 2016 ; Alvarez-Flores et al, 2019 ). The protein was therefore indicated by these authors as a promising molecule for the development of new formulations for wound healing.…”

“…In this regard, the ability of the crude bristle extract of Lonomia obliqua to modulate inflammatory markers was recently demonstrated in a human macrophage model ( Oliveira et al, 2021 ). As Lopap has previously been shown not to exert pro-inflammatory activity ( Fritzen et al, 2005 ; Waismam et al, 2009 ) and, as with Losac, Lopap-derived peptides provide cytoprotective activity ( Chudzinski-Tavassi et al, 2010 ; Carrijo-Carvalho et al, 2012 ; Wlian et al, 2014 ; Alvarez-Flores et al, 2021 ) and improve wound healing ( Sato et al, 2016 ), we investigated the effect of these recombinant proteins in myoblast cells upon inflammatory stimulus by IL-1β. Interestingly, we found that both proteins exerted anti-inflammatory effects: they were able to inhibit the production of PGE 2 and IL-6 induced by IL-1β.…”

“…Besides its important myogenic activity, PGE 2 is a major pro-inflammatory mediator, associated with the potentiation of pain, vasodilation and oedema. IL-6, in turn, is a ubiquitously expressed cytokine that can have pro- and anti-inflammatory effects, depending on the concentration and local tissue environment ( Sato et al, 2016 ). It is released during inflammatory processes and contributes not only to the immune response but also to the activation of metabolic and catabolic pathways, leading to a decrease in skeletal muscle mass ( Belizário et al, 2016 ).…”

“…Its recombinant form–rLosac–inhibited the apoptosis of human fibroblasts and promoted cell survival in mouse cortical neurons ( Bosch et al, 2016 ; Alvarez-Flores et al, 2019 ). It also improved wound healing in an in vivo model of a skin wound by preserving the extracellular matrix organization, including collagen type I, fibronectin and laminin expression ( Sato et al, 2016 ). Lopap, in turn, belongs to the lipocalin family of proteins.…”

From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery

“…Caterpillars from different South American countries, such as Venezuela, Brazil, French Guyana, Peru, Paraguay, Argentina and Colombia, are responsible for a severe bleeding syndrome in humans who touch their bristles (Arocha-Pinango and Guerrero, 2001). Lonomia obliqua is the main species of caterpillar found in Southern Brazil and its venom is comprised of molecules with antiviral, procoagulant, fibrinolytic and wound healing activities (Veiga et al, 2005;Reis et al, 2006;Alvarez-Flores et al, 2011;Carmo et al, 2015;Sato et al, 2016). Their toxic compounds are found in the bristle extract, hemolymph, cryosecretion (a crude venomous fluid ejected by the whole secretory tegument of caterpillars, stored at -20°C for 24 h) and tegument extract (Pinto et al, 2006;Veiga et al, 2009).…”