title: 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.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
authors.forename: Puebla
authors.initials: P
authors.lastname: Cassini-Vieira
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
authors.forename: Mariane
authors.initials: M
authors.lastname: Felipetto
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
authors.forename: Leandro Barbosa
authors.initials: LB
authors.lastname: Prado
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Verano-Braga
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
authors.forename: Silvia Passos
authors.initials: SP
authors.lastname: Andrade
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
authors.forename: Robson A S
authors.initials: RAS
authors.lastname: Santos
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: de Lima
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil.
authors.forename: Adriano M C
authors.initials: AMC
authors.lastname: Pimenta
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Minas Gerais, Brazil. Electronic address: luciolasbarcelos@gmail.com.
authors.forename: Luciola Silva
authors.initials: LS
authors.lastname: Barcelos
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D004987:Ethers; D006097:Granulation Tissue / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011140:Polyurethanes; D012604:Scorpion Venoms / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D015415:Biomarkers; D004987:Ethers; D011140:Polyurethanes; D012604:Scorpion Venoms; C000627931:Ts14 toxin; Tityus serrulatus; D003094:Collagen
keywords: Angiogenesis; Bradykinin-potentiating peptide; Fibrogenesis; Inflammation; Tityus serrulatus; Ts14; TsHpt-I (Tityus serrulatus Hypotensin-I)