Purinergic P2X4 Receptor

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Kazuhide Inoue - One of the best experts on this subject based on the ideXlab platform.

  • Transcription factor IRF5 drives P2X4R^+-reactive microglia gating neuropathic pain
    Nature Communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain. In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of proteins, such as the Purinergic P2X4 Receptor. Here, Masuda et al. show that the transcription factor axis, interferon regulatory factor-8 and -5, drives the expression of P2X4 Receptor in microglia and the adoption of a reactive phenotype after peripheral nerve injury.

  • Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain.
    Nature communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain.

Takahiro Masuda - One of the best experts on this subject based on the ideXlab platform.

  • Transcription factor IRF5 drives P2X4R^+-reactive microglia gating neuropathic pain
    Nature Communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain. In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of proteins, such as the Purinergic P2X4 Receptor. Here, Masuda et al. show that the transcription factor axis, interferon regulatory factor-8 and -5, drives the expression of P2X4 Receptor in microglia and the adoption of a reactive phenotype after peripheral nerve injury.

  • Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain.
    Nature communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain.

Akira Nishiyama - One of the best experts on this subject based on the ideXlab platform.

  • Transcription factor IRF5 drives P2X4R^+-reactive microglia gating neuropathic pain
    Nature Communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain. In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of proteins, such as the Purinergic P2X4 Receptor. Here, Masuda et al. show that the transcription factor axis, interferon regulatory factor-8 and -5, drives the expression of P2X4 Receptor in microglia and the adoption of a reactive phenotype after peripheral nerve injury.

  • Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain.
    Nature communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain.

Makoto Tsuda - One of the best experts on this subject based on the ideXlab platform.

  • Transcription factor IRF5 drives P2X4R^+-reactive microglia gating neuropathic pain
    Nature Communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain. In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of proteins, such as the Purinergic P2X4 Receptor. Here, Masuda et al. show that the transcription factor axis, interferon regulatory factor-8 and -5, drives the expression of P2X4 Receptor in microglia and the adoption of a reactive phenotype after peripheral nerve injury.

  • Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain.
    Nature communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain.

Tomohiko Tamura - One of the best experts on this subject based on the ideXlab platform.

  • Transcription factor IRF5 drives P2X4R^+-reactive microglia gating neuropathic pain
    Nature Communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain. In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of proteins, such as the Purinergic P2X4 Receptor. Here, Masuda et al. show that the transcription factor axis, interferon regulatory factor-8 and -5, drives the expression of P2X4 Receptor in microglia and the adoption of a reactive phenotype after peripheral nerve injury.

  • Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain.
    Nature communications, 2014
    Co-Authors: Takahiro Masuda, Shosuke Iwamoto, Ryohei Yoshinaga, Hidetoshi Tozaki-saitoh, Akira Nishiyama, Tak W. Mak, Tomohiko Tamura, Makoto Tsuda, Kazuhide Inoue
    Abstract:

    In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of different sets of genes. Spinal microglia expressing the Purinergic P2X4 Receptor (P2X4R) after peripheral nerve injury (PNI) are implicated in neuropathic pain. Here we show that interferon regulatory factor-5 (IRF5), which is induced in spinal microglia after PNI, is responsible for direct transcriptional control of P2X4R. Upon stimulation of microglia by fibronectin, IRF5 induced de novo expression of P2X4R by directly binding to the promoter region of the P2rx4 gene. Mice lacking Irf5 did not upregulate spinal P2X4R after PNI, and also exhibited substantial resistance to pain hypersensitivity. Furthermore, we found that expression of IRF5 in microglia is regulated by IRF8. Thus, an IRF8-IRF5 transcriptional axis may contribute to shifting spinal microglia toward a P2X4R-expressing reactive state after PNI. These results may provide a new target for treating neuropathic pain.