Aliskiren Attenuates the Inflammatory Response and Wound Healing Process in Diabetic Mice With Periodontal Disease

Autor(es)

Penha Oliveira, Sandra Helena ^{[1, 2]} ; Balera Brito, Victor Gustavo ^{[1, 2]} ; Tfaile Frasnelli, Sabrina Cruz ^[1] ; Ribeiro, Bianca da Silva ^[1] ; Ferreira, Milena Nunes ^[1] ; Queiroz, Dayane Priscilla ^{[1, 2]} ; Beltan, Carluci Tais ^[1] ; Lara, Vanessa Soares ^[3] ; Santos, Carlos Ferreira ^[4]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Dent Aracatuba, Dept Basic Sci, Sao Paulo - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Dent Aracatuba, Programa Multictr Posgrad Ciencias Fisiol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Bauru Sch Dent, Dept Stomatol, Bauru - Brazil

^[4] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Bauru - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN PHARMACOLOGY; v. 10, JUL 4 2019.
• Citações Web of Science: 1

Resumo

The aim of this study was to characterize the role of local RAS (renin-angiotensin system) in the inflammatory response of normal (N) and diabetic (D) mice with periodontal disease (PD). Diabetes Mellitus (DM) was induced by peritoneal injection of streptozotocin in Balb/c mice. PD was induced by ligature around the first molar in both N and D, irrespective of whether they were treated with aliskiren (50 mg/kg, Alisk). Mandibles were harvested for histomorphometric analyses, and gingival tissue (GT) was collected to evaluate gene expression and extracellular matrix components (ECM). Immunohistochemical (IHC) analyses were used to localize RAS in GT. The production of C-reactive protein (CRP), IL-1 beta, CXCL2, and CCL8 was evaluated by enzyme-linked immunosorbent assay (ELISA). Renin was found to exacerbate the inflammation and periodontal bone loss at 14 days after PD, and Alisk inhibited this process in GT of N and D. PD increased CRP, CXCL2, CCL8, and IL-1 beta production in both animals. Alisk could inhibit CRP, CXCL2, and CCL8 primarily in D animals. However, only CCL8 was decreased in N animals after Alisk pretreatment. PD enhanced expression and production of AGT, ACE, AT1R, and AT2R in both N and D. AT1R expression was higher in D with PD, and AT2R expression was higher in N with PD. ACE2 and receptor Mas (MasR) expression and production was elevated in the control group of both animals. PD inhibited ACE2 in N but not in D. MasR expression was unaffected in both N and D with PD. Alisk reduced expression and production of all RAS components in GT of both animals, except for ACE2 in N. RAS staining was observed in all layers of epithelium, basal cell layer, and lamina propria and was higher in N with PD. Col1a1, Col1a2, Col3a1, and fibronectin (Fn1) were increased in both animals with PD. Alisk inhibited Col1a1 and Fn in both animals, Col1a2 was decreased only in D, while levels of Col3a1 remained unchanged in all animal groups. In conclusion, these data demonstrated the presence and functional role of local RAS in GT, exacerbating the inflammatory response, periodontal bone loss, and wound healing processes in both N and D animal groups. In addition, Alisk was able to significantly reduce gingival inflammation, excessive wound healing processes, and periodontal bone loss. (AU)

• Processo FAPESP: 18/04989-0 - Papel dos mastócitos e seus microRNAs sobre a resposta inflamatória e metabolismo ósseo em camundongos diabéticos com periodontite
• Beneficiário: Milena Nunes Ferreira
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 17/05873-3 - Análise in vitro do papel dos mastócitos e do sistema renina-angiotensina sobre osteoblastos e osteoclastos de animais espontaneamente hipertensos
• Beneficiário: Sabrina Cruz Tfaile Frasnelli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/04476-3 - Papel da renina sobre a produção de citocinas Th17, estresse oxidativo e antioxidantes pelo tecido gengival de camundongos diabéticos com periodontite
• Beneficiário: Bianca da Silva Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/03965-2 - Papel do sistema renina-angiotensina em diferentes modelos inflamatórios orais: uma abordagem interdisciplinar experimental e clínica
• Beneficiário: Carlos Ferreira dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Temático