Ts14 from Tityus serrulatus boosts angiogenesis and attenuates inflammation and collagen deposition in sponge-induced granulation tissue in mice

Abstract

We have previously described a 25mer anti-hypertensive peptide, previously named TsHpt-I (Tityus serrulatus Hypotensin-I), now Ts14, as an agonist of B2 kinin receptor. Bradykinin is known to play physiological roles in angiogenic, inflammatory, and fibrogenic processes, mostly mediated by B2 receptor. Therefore, we investigated whether Ts14 could modulate key events (neovascularization, inflammatory cell recruitment, and extracellular matrix deposition) of the fibrovascular tissue, induced by polyether-polyurethane sponge implants in mice. Sponges were implanted in the dorsum of 7-week-old C57Bl/6 male mice that received daily intrasponge treatment with Ts14 (27.25μg/sponge/day in 10μL PBS) or vehicle (10μL PBS/sponge/day) and were assessed on day 7 after surgery. Hemoglobin content, blood flow (laser Doppler perfusion imaging), and VEGF levels in the implants, used as indices of vascularization, indicated that Ts14 enhanced angiogenesis in implants relative to the PBS-treated group. Interestingly, Ts14 reduced TNF-α levels and neutrophil infiltration, although stimulated macrophage infiltration into implants, as determined by myeloperoxidase (MPO) and N-acetyl-β-d-glucosaminidase (NAG) enzyme activities, respectively. Regarding the fibrogenic component (soluble collagen content and Sirius-red histological staining), we observed that Ts14 inhibited collagen deposition in the implants. Overall, our results suggest that Ts14 exerts proangiogenic, anti-inflammatory, and anti-fibrogenic activities. These effects may indicate a therapeutical potential of this peptide in conditions where angiogenesis, inflammation, and fibrogenesis contribute to disease progression and chronicity.