Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium

Terenzi, Riccardo; Manetti, Mirko; Rosa, Irene; Romano, Eloisa; Galluccio, Felice; Guiducci, Serena; Ibba‐Manneschi, Lidia; Matucci‐Cerinic, Marco

doi:10.1038/s41598-017-13746-w

Cited by 45 publications

(33 citation statements)

References 42 publications

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“… 26 Interestingly, activation of AT 2 R or HGF/c-Met signalling was revealed to suppress the inflammatory response in different tissues. 27 – 30 Therefore, whether AT 2 R or HGF/c-Met signalling was involved in the anti-inflammatory properties of Ang IV under the context of CCH deserves further investigation in the future.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin IV suppresses inflammation in the brains of rats with chronic cerebral hypoperfusion

Wang

Xue

Yang

et al. 2018

J Renin Angiotensin Aldosterone Syst

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Introduction:This study aimed to evaluate the influence of central angiotensin IV (Ang IV) infusion on chronic cerebral hypoperfusion (CCH)-related neuropathological changes including amyloid-β (Aβ), hyperphosphorylated tau (p-tau) and the inflammatory response.Materials and methods:Rats with CCH received central infusion of Ang IV, its receptor AT4R antagonist divalinal-Ang IV or artificial cerebrospinal fluid for six weeks. During this procedure, the systolic blood pressure (SBP) was monitored, and the levels of Aβ42, p-tau and pro-inflammatory cytokines in the brain were detected.Results:Rats with CCH exhibited higher levels of Aβ42, p-tau and pro-inflammatory cytokines in the brain when compared with controls. Infusion of Ang IV significantly reduced the expression of pro-inflammatory cytokines in the brains of rats with CCH. Meanwhile, the reduction of pro-inflammatory cytokines levels caused by Ang IV was reversed by divalinal-Ang IV. During the treatment, the SBP in rats was not significantly altered.Conclusion:This study demonstrates for the first time that Ang IV dose-dependently suppresses inflammation through AT4R in the brains of rats with CCH, which is independent from SBP. These findings suggest that Ang IV/AT4R may represent a potential therapeutic target for CCH-related neurological diseases.

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Section: Discussionmentioning

confidence: 99%

Angiotensin IV suppresses inflammation in the brains of rats with chronic cerebral hypoperfusion

Wang

Xue

Yang

et al. 2018

J Renin Angiotensin Aldosterone Syst

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“…Immunohistochemistry was carried out on formalin-fixed and paraffin-embedded synovial tissue blocks following previously established protocols 44 , 47 , 64 . Synovial sections (5 µm thick) were deparaffinized, boiled for 10 minutes in sodium citrate buffer (10 mM, pH 6.0) for antigen unmasking and then treated with 3% H 2 O 2 solution for 15 minutes at room temperature to block endogenous peroxidases.…”

Section: Methodsmentioning

confidence: 99%

“…Phase-contrast images were obtained under a Leica inverted microscope (Leica Microsystems) to assess cell morphology. Fluorescence immunocytochemistry was carried out as reported elsewhere 64 . Briefly, cells were grown onto glass coverslips, fixed with 3.7% buffered paraformaldehyde and then permeabilized with 0.1% Triton X-100 in PBS.…”

Section: Methodsmentioning

confidence: 99%

Morphological evidence of telocytes in human synovium

Rosa

Marini

Guasti

et al. 2018

Sci Rep

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A new cell type named telocyte (i.e. cell with distinctive prolongations called telopodes) has recently been identified in the stroma of various organs in humans. However, no study has yet reported the existence of telocytes in the synovial membrane of diarthrodial joints. This work was therefore undertaken to search for telocytes in the normal human synovium using transmission electron microscopy, immunohistochemistry and immunofluorescence. Ultrastructural analyses demonstrated the presence of numerous spindle-shaped telocytes in the whole synovial sublining layer. Synovial telocytes exhibited very long and thin moniliform telopodes and were particularly concentrated at the boundary between the lining and sublining layers and around blood vessels. Light microscopy confirmed the presence of CD34-positive telocytes in the aforementioned locations. Moreover, synovial telocytes coexpressed CD34 and platelet-derived growth factor receptor α. Double immunostaining further allowed to unequivocally differentiate synovial telocytes (CD34-positive/CD31-negative) from vascular endothelial cells (CD34-positive/CD31-positive). The in vitro examination of fibroblast-like synoviocyte primary cultures revealed the coexistence of different cell types, including CD34-positive telocytes projecting typical moniliform telopodes. In conclusion, our work provides the first evidence that telocytes do exist in the human synovium and lays the groundwork for future studies on synovial telocytes in a variety of degenerative and destructive joint diseases.

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“…The protective effect of TELM observed herein could have been associated with the amount of cytokine production in the local lesion. The expression of At2r, which has already been associated with anti-inflammatory effects and tissue repair in different animal models (Namsolleck et al, 2014;Terenzi et al, 2017), was reduced following the induction of PD only in the W group and was similar to that of hypertensive animals following the induction of PD. However, the reduction in the expression of Atr was reversed by TELM in Wistar rats.…”

Section: Discussionmentioning

confidence: 56%

Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease

et al. 2020

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Periodontal disease (PD) is a prevalent inflammatory disease with the most severe consequence being the loss of the alveolar bone and teeth. We therefore aimed to evaluate the effects of telmisartan (TELM), an angiotensin II type 1 receptor (Agtr1) antagonist, on the PD-induced alveolar bone loss, in Wistar (W) and Spontaneous Hypertensive Rats (SHRs). PD was induced by ligating the lower first molars with silk, and 10 mg/kg TELM was concomitantly administered for 15 days. The hemimandibles were subjected to microtomography, ELISA was used for detecting tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), CXCL3, and CCL2, while qRT-PCR was used for analyzing expression of components of renin-angiotensin system (RAS) (Agt, Ace, Agt1r, Agt2r, Ace2, and Masr), and bone markers (Runx2, Osx, Catnb, Alp, Col1a1, Opn, Ocn, Bsp, Bmp2, Trap, Rank, Rankl, CtsK, Mmp-2, Mmp-9, and osteoclast-associated receptor (Oscar)). The SHR + PD group showed greater alveolar bone loss than the W + PD group, what was significantly inhibited by treatment with TELM, especially in the SHR group. Additionally, TELM reduced the production of TNF-α, IL-1β, and CXCL3 in the SHR group. The expression of Agt increased in the groups with PD, while Agtr2 reduced, and TELM reduced the expression of Agtr1 and increased the expression of Agtr2, in W and SHRs. PD did not induce major changes in the expression of bone formation markers, except for the expression of Alp, which decreased in the PD groups. The bone resorption markers expression, Mmp9, Ctsk, and Vtn, was higher in the SHR + PD group, compared to the respective control and W + PD group. However, TELM attenuated these changes and increased the expression of Runx2 and Alp. Our study suggested that TELM has a protective effect on the progression of PD, especially in hypertensive animals, as evaluated by the resorption of the lower alveolar bone. This can be partly explained by the modulation in the expression of Angiotensin II receptors (AT1R and AT2R), reduced production of inflammatory mediators, the reduced expression of resorption markers, and the increased expression of the bone formation markers.

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Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium

Cited by 45 publications

References 42 publications

Angiotensin IV suppresses inflammation in the brains of rats with chronic cerebral hypoperfusion

Angiotensin IV suppresses inflammation in the brains of rats with chronic cerebral hypoperfusion

Morphological evidence of telocytes in human synovium

Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease

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