Pore‐forming toxin‐like protein complex expressed by frog promotes tissue repair

Abstract

Tissue repair is a highly dynamic process, and the immediate onset of acute inflammation has been considered necessary for repair. Pore-forming proteins are important, both in pathogen invasion and host immunity. However, their roles in wound healing and tissue repair are unclear. βγ-crystallin fused aerolysin-like protein (α-subunit) and trefoil factor (β-subunit) complex (βγ-CAT) is a complex of a bacterial pore-forming toxin aerolysin-like protein and trefoil factor identified in the frog Bombina maxima. In this study, we established mouse cutaneous wound models to explore the effects of βγ-CAT on skin wound healing. βγ-CAT accelerated the healing of full-thickness wounds by improving re-epithelialization. This complex relieved dermal edema and promoted scarless healing. βγ-CAT treatment resulted in a rapid release of IL-1β, which initiated an acute inflammation response in the early stage of healing. Meanwhile, the expression levels of TGF-β1, VEGF, and bFGF and the recruitment of M2 macrophages around the wound significantly increased after βγ-CAT treatment. βγ-CAT protected skin wounds against methicillin-resistant Staphylococcus aureus by improving neutrophil recruitment at the site of the wound. Overall, our results suggest that βγ-CAT can promote tissue repair and protect skin wounds against antibiotic-resistant bacterial infection by triggering the acute inflammatory response. This is the first example that aerolysin-like pore-forming proteins widely existing in plants and animals may act in wound healing and tissue repair.-Gao, Z.-H., Deng, C.-J., Xie, Y.-Y., Guo, X.-L., Wang, Q.-Q., Liu, L.-Z., Lee, W.-H., Li, S.-A., Zhang, Y. Pore-forming toxin-like protein complex expressed by frog promotes tissue repair.

A secreted pore‐forming protein modulates cellular endolysosomes to augment antigen presentation

“…After washed cells three times with PBS, the cells were cocultured with purified CD3 + T cells for 16 hours. To harvest T cells activated by EVs derived from BMDCs, EVs were harvested from the supernatants of that BMDCs stimulated with PBS, OVA (20 μg/mL), OVA plus βγ-CAT (10 nM), βγ-CAT alone, or heat-inactivated βγ-CAT (pretreated βγ-CAT at 60℃ for 30 minutes as previously described 25 ) for 4 hours. EVs were incubated with purified CD3 + T cells for 16 hours.…”

“…24 Previous studies have illustrated its roles in frog innate immunity and tissue repair. [24][25][26][27] βγ-CAT exerts its cellular effects by targeting the acidic glycosphingolipids in lipid rafts of the cell plasma membrane via a double-receptor binding model to initiate the endocytosis of its α-subunit BmALP1, 28 and the subsequent oligomerization and pore formation of BmALP1 on cellular endolysosomes through endocytic pathways, 24,27 which is negatively regulated by paralog of βγ-CAT in a redox-dependent manner. 29 This process modulates the content and biochemical properties of these intracellular vesicles, leading to various cellular responses and outcomes depending on different cell contexts.…”

Ketogenic diet promotes apoptosis of tumor cells and inhibits tumor growth through inhibiting Wnt1/β-catenin signaling pathway in mouse xenograft models of human colon cancer

“…Immunohistochemistry was applied to detect the expression of Wnt1/β-catenin signaling proteins of subcutaneous tumors and performed according to a method described previously [26]. Brie y, the above prepared tumor sections were depara nized with xylene and rehydrated with a series of concentrations of ethanol, then antigen repair was performed with 10 mM citrate buffer at pH 6.0.…”

Bv8-Like Toxin from the Frog Venom of Amolops jingdongensis Promotes Wound Healing via the Interleukin-1 Signaling Pathway

“…βγ-crystallin fused aerolysin-like protein (α-subunit) and trefoil factor (β-subunit) complex (βγ-CAT) is a complex of a bacterial pore-forming toxin aerolysin-like protein and trefoil factor identified in the frog Bombina maxima. βγ-CAT treatment increased the expression of IL-1β, TGF-β1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and accelerated the healing of full-thickness wounds [21]. Our present study reveals that Bv8-AJ, a novel Bv8-like peptide, exerted strong proliferative effect on KC and FB by activating IL-1 production via MAPK signaling pathway.…”

“…Over recent years, a number of amphibian peptides such as AH90, βγ-CAT, Ot-WHP, CW49, and Bm-TFF2 has been discovered and they have been reported to play important roles in angiogenesis and wound healing [20][21][22][23][24]. AH90 was identified from skin secretions of frog Odorrana grahami.…”