Chronic nerve injury-induced Mas receptor expression in dorsal root ganglion neurons alleviates neuropathic pain

Zhao, Yuan-Ting; Qin, Yue; Liu, Tuan-Jiang; Hao, Dingjun

doi:10.3892/etm.2015.2801

Cited by 24 publications

(17 citation statements)

References 24 publications

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“…This rather indicates that both antagonists target the same receptor in human VSMC and that a unique Mas subtype receptor thus mediates the anti-inflammatory effects of Ang-(1-7) in this cell type. Indeed, our findings are in line with other reports identifying a single Mas receptor, sensitive to both D-Pro 7 -Ang-(1-7) and A779 antagonism, mediating the vasorelaxant action of Ang-(1-7) in murine conductance and resistance arteries (Lemos et al, 2005; Peiró et al, 2013) as well as other non-vascular actions of the heptapeptide (Zhao et al, 2015). …”

Section: Discussionsupporting

confidence: 93%

The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells

et al. 2016

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Background and Aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7) is a member of the renin-angiotensin system (RAS) that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7) to counteract human aortic smooth muscle cell (HASMC) inflammation triggered by RAS-dependent and -independent stimuli, such as Ang II or interleukin (IL)-1β.Methods and Results: In cultured HASMC, the expression of inducible nitric oxide synthase (iNOS) and the release of nitric oxide were stimulated by both Ang II and IL-1β, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7) in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7), suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and nuclear factor (NF)-κB. Indeed, Ang-(1-7) markedly inhibited the activation of the NADPH oxidase and subsequently of NF-κB, as determined by lucigenin-derived chemiluminescence and electromobility shift assay, respectively.Conclusion: Ang-(1-7) can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7)/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

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Section: Discussionsupporting

confidence: 93%

The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells

et al. 2016

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“…There is evidence that the Mas receptor increases mRNA and protein expression in corresponding DRG after chronic constriction injury to the sciatic nerve and that Ang-(1-7) significantly inhibits neuropathic pain in chronic constriction injury. 79 In a model of prostaglandin-induced hyperalgesia, Ang-(1-7) dose-dependently attenuated behavioral signs of pain. 7,9,41 Because of the inflammatory and neuropathic characteristics of bone cancer pain, we chose to investigate the utility of Ang-(1-7) in CIBP.…”

Section: Discussionmentioning

confidence: 98%

Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain

Forte

Slosky

Zhang

et al. 2016

Pain

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“…Chronic nerve injury‐induced neuropathic pain was shown to be attenuated by the i.t. administration of Ang (1‐7) and signalling via spinal Mas receptors (Zhao et al, ). In the present study, we showed for the first time that the i.t.…”

Section: Discussionmentioning

confidence: 99%

Anti‐hypersensitive effect of angiotensin (1‐7) on streptozotocin‐induced diabetic neuropathic pain in mice

Okita

Nemoto

Yamagata

et al. 2018

European Journal of Pain

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Background We have recently reported that the spinal angiotensin (Ang) converting enzyme (ACE)/Ang II/AT1 receptor axis and downstream p38 MAPK phosphorylation are activated in streptozotocin (STZ)‐induced diabetic mice and lead to tactile hypersensitivity. Moreover, our previous results suggested that the intrathecal (i.t.) administration of Ang (1‐7), an N‐terminal fragment of Ang II, may attenuate the Ang II‐induced nociceptive behaviour through the inhibition of p38 MAPK phosphorylation via Mas receptors. Here, we investigated whether the i.t. administration of Ang (1‐7) can attenuate STZ‐induced diabetic neuropathic pain. Methods Tactile and thermal hypersensitivities were determined using the von Frey filament and Hargreaves tests, respectively. The protein expression of ACE2, Mas receptors and phospho‐p38 MAPK was measured by western blotting. Spinal ACE2 activity was determined using ACE2 activity assay kit. Results The i.t. administration of Ang (1‐7) significantly reduced the tactile and thermal hypersensitivities on day 14 after STZ injection, and these effects were significantly prevented by the Mas receptor antagonist A779. The expression of ACE2 and Mas receptors in the plasma membrane fraction of the lumbar dorsal spinal cord was both significantly decreased in STZ mice. Spinal ACE2 activity was also decreased while p38 MAPK phosphorylation was increased in the lumbar dorsal region of these mice. This phosphorylation was attenuated by the injection of Ang (1‐7), whose effect was reversed by A779. Conclusions Our data demonstrate that Ang (1‐7) attenuates STZ‐induced diabetic neuropathic pain and that this occurs through a mechanism involving spinal Mas receptors and he inhibition of p38 MAPK phosphorylation. Significance The ACE2/Ang (1‐7)/Mas receptor axis was down‐regulated in the spinal cord of STZ mice and the i.t. administration of Ang (1‐7) attenuated the STZ‐induced diabetic neuropathic pain via Mas receptors. Therefore, the activation of this axis could be an effective therapeutic target to alleviate the neuropathic pain in diabetic patients.

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Chronic nerve injury-induced Mas receptor expression in dorsal root ganglion neurons alleviates neuropathic pain

Cited by 24 publications

References 24 publications

The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells

The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells

Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain

Anti‐hypersensitive effect of angiotensin (1‐7) on streptozotocin‐induced diabetic neuropathic pain in mice

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