Limits...
Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue.

Santos CF, Morandini AC, Dionísio TJ, Faria FA, Lima MC, Figueiredo CM, Colombini-Ishikiriama BL, Sipert CR, Maciel RP, Akashi AP, Souza GP, Garlet GP, Rodini CO, Amaral SL, Becari C, Salgado MC, Oliveira EB, Matus I, Didier DN, Greene AS - PLoS ONE (2015)

Bottom Line: However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts.Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin.Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.

ABSTRACT
The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

No MeSH data available.


Related in: MedlinePlus

Renin-Angiotensin System Components in Human Gingiva.A) qPCR analysis of the following RAS components extracted from human gingiva from healthy (open bars), gingivitis (gray bars) and periodontitis (black bars) groups: angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE-2), renin, angiotensin II receptor type 1 (AT1R), and Mas receptor (MasR), (n = 7). Graphs displays relative expression levels of the target mRNA relative to RPL-13 mRNA. The means were compared using a 1-way ANOVA and Tukey’s test. B) Immunoreactivity of AT1R and AT2R in the gingiva from healthy volunteers (open bars) and volunteers with gingivitis and periodontitis combined (black bars). The means were compared using a 1-way ANOVA and Ang with gingivitis and periodontitis is indicated by *. C) Representative photographs of immunoreactivity for either AT1R (Ca and Ce) or AT2R (Ce and Cf) in the gingiva from either healthy volunteers (Ca and Cd) or volunteers with gingivitis and periodontitis (Ce and Cf). Photographs Cb and Cd are from tissue incubated with nonimmune serum in Healthy Tissue. Scale bars indicate a distance of 20μm.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4526652&req=5

pone.0134601.g002: Renin-Angiotensin System Components in Human Gingiva.A) qPCR analysis of the following RAS components extracted from human gingiva from healthy (open bars), gingivitis (gray bars) and periodontitis (black bars) groups: angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE-2), renin, angiotensin II receptor type 1 (AT1R), and Mas receptor (MasR), (n = 7). Graphs displays relative expression levels of the target mRNA relative to RPL-13 mRNA. The means were compared using a 1-way ANOVA and Tukey’s test. B) Immunoreactivity of AT1R and AT2R in the gingiva from healthy volunteers (open bars) and volunteers with gingivitis and periodontitis combined (black bars). The means were compared using a 1-way ANOVA and Ang with gingivitis and periodontitis is indicated by *. C) Representative photographs of immunoreactivity for either AT1R (Ca and Ce) or AT2R (Ce and Cf) in the gingiva from either healthy volunteers (Ca and Cd) or volunteers with gingivitis and periodontitis (Ce and Cf). Photographs Cb and Cd are from tissue incubated with nonimmune serum in Healthy Tissue. Scale bars indicate a distance of 20μm.

Mentions: The mRNAs for RAS components (AGT, renin, ACE, ACE-2, AT1R, and MasR) were expressed in the gingiva of volunteers from all three groups. No differences in the expression of mRNAs among all three groups were found when compared within each mRNA target (Fig 2A). In particular, the mRNA expression for the AT1R in gingiva was not different among the healthy, gingivitis and periodontitis groups 1.6 (±1.0), 1.4 (±1.7) and 0.9 (±1.7) respectively; likewise the mRNA expression for the MasR was not different among the gingiva from the healthy group, gingivitis group and periodontitis group, 1.0 (±1.5), 1.0 (±2.1) and 0.6 (±1.6) respectively (Fig 2A). Additionally, among each group of volunteers no differences were found in the expression of the mRNAs for AGT, ACE, ACE-2 and renin (Fig 2A).


Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue.

Santos CF, Morandini AC, Dionísio TJ, Faria FA, Lima MC, Figueiredo CM, Colombini-Ishikiriama BL, Sipert CR, Maciel RP, Akashi AP, Souza GP, Garlet GP, Rodini CO, Amaral SL, Becari C, Salgado MC, Oliveira EB, Matus I, Didier DN, Greene AS - PLoS ONE (2015)

Renin-Angiotensin System Components in Human Gingiva.A) qPCR analysis of the following RAS components extracted from human gingiva from healthy (open bars), gingivitis (gray bars) and periodontitis (black bars) groups: angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE-2), renin, angiotensin II receptor type 1 (AT1R), and Mas receptor (MasR), (n = 7). Graphs displays relative expression levels of the target mRNA relative to RPL-13 mRNA. The means were compared using a 1-way ANOVA and Tukey’s test. B) Immunoreactivity of AT1R and AT2R in the gingiva from healthy volunteers (open bars) and volunteers with gingivitis and periodontitis combined (black bars). The means were compared using a 1-way ANOVA and Ang with gingivitis and periodontitis is indicated by *. C) Representative photographs of immunoreactivity for either AT1R (Ca and Ce) or AT2R (Ce and Cf) in the gingiva from either healthy volunteers (Ca and Cd) or volunteers with gingivitis and periodontitis (Ce and Cf). Photographs Cb and Cd are from tissue incubated with nonimmune serum in Healthy Tissue. Scale bars indicate a distance of 20μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526652&req=5

pone.0134601.g002: Renin-Angiotensin System Components in Human Gingiva.A) qPCR analysis of the following RAS components extracted from human gingiva from healthy (open bars), gingivitis (gray bars) and periodontitis (black bars) groups: angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE-2), renin, angiotensin II receptor type 1 (AT1R), and Mas receptor (MasR), (n = 7). Graphs displays relative expression levels of the target mRNA relative to RPL-13 mRNA. The means were compared using a 1-way ANOVA and Tukey’s test. B) Immunoreactivity of AT1R and AT2R in the gingiva from healthy volunteers (open bars) and volunteers with gingivitis and periodontitis combined (black bars). The means were compared using a 1-way ANOVA and Ang with gingivitis and periodontitis is indicated by *. C) Representative photographs of immunoreactivity for either AT1R (Ca and Ce) or AT2R (Ce and Cf) in the gingiva from either healthy volunteers (Ca and Cd) or volunteers with gingivitis and periodontitis (Ce and Cf). Photographs Cb and Cd are from tissue incubated with nonimmune serum in Healthy Tissue. Scale bars indicate a distance of 20μm.
Mentions: The mRNAs for RAS components (AGT, renin, ACE, ACE-2, AT1R, and MasR) were expressed in the gingiva of volunteers from all three groups. No differences in the expression of mRNAs among all three groups were found when compared within each mRNA target (Fig 2A). In particular, the mRNA expression for the AT1R in gingiva was not different among the healthy, gingivitis and periodontitis groups 1.6 (±1.0), 1.4 (±1.7) and 0.9 (±1.7) respectively; likewise the mRNA expression for the MasR was not different among the gingiva from the healthy group, gingivitis group and periodontitis group, 1.0 (±1.5), 1.0 (±2.1) and 0.6 (±1.6) respectively (Fig 2A). Additionally, among each group of volunteers no differences were found in the expression of the mRNAs for AGT, ACE, ACE-2 and renin (Fig 2A).

Bottom Line: However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts.Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin.Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.

ABSTRACT
The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

No MeSH data available.


Related in: MedlinePlus