Expression profiles of TRPV1, TRPV4, TLR4 and ERK1/2 in the dorsal root ganglionic neurons of a cancer-induced neuropathy rat model

Maqboul, Ahmad; Elsadek, Bakheet

doi:10.7717/peerj.4622

Cited by 20 publications

(12 citation statements)

References 53 publications

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“…Another study showed TRPV4 regulates breast cancer cell migration by increasing cell deformability 23 . TRPV4 changes expression in dorsal root ganglia after cancer cell inoculation and may play a role in transducing cancer-induced hyperalgesia 24 . Our study demonstrated that TRPV4 mediated glioma cell migration and invasion, which strengthens the idea that TRPV4 is essential for tumor invasiveness.…”

Section: Discussionmentioning

confidence: 99%

TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions

Yang

et al. 2020

Sci Rep

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The invasion ability of glioblastoma (GBM) causes tumor cells to infiltrate the surrounding brain parenchyma and leads to poor outcomes. Transient receptor potential vanilloid 4 (TRPV4) exhibits a remarkable role in cancer cell motility, but the contribution of TRPV4 to glioblastoma metastasis is not fully understood. Here, we reported that TRPV4 expression was significantly elevated in malignant glioma compared to normal brain and low-grade glioma, and TRPV4 expression was negatively correlated with the prognosis of glioma patients. Functionally, stimulation of TRPV4 promoted glioblastoma cell migration and invasion, and repression of TRPV4 hindered the migration and invasion of glioblastoma cells in vitro. Molecularly, TRPV4 strongly colocalized and interacted with skeletal protein-F-actin at cellular protrusions, and TRPV4 regulated the formation of invadopodia and filopodia in glioblastoma cells. Furthermore, the Cdc42/N-wasp axis mediated the effect of TRPV4regulated cellular protrusions and invasion. Foremost, TRPV4 inhibitor treatment or downregulation of TRPV4 significantly reduced the invasion-growth of subcutaneously and intracranially transplanted glioblastoma in mice. In conclusion, the TRPV4/Cdc42/wasp signaling axis regulates cellular protrusion formation in glioblastoma cells and influences the invasion-growth phenotype of glioblastoma in vivo. TRPV4 may serve as a prognostic factor and specific therapeutic target for GBM patients. Abbreviations Cdc42 Cell division cycle 42 N-wasp Neural Wiskott-Aldrich syndrome proteins mDIA Mammalian homolog of diaphanous WAVE Wiskott-Aldrich syndrome protein family verprolin homologous protein CHO cell Chinese hamster ovary cell DRG cell Dorsal root ganglia cell RTVP-1 Related to testis-specific, vespid and pathogenesis protein 1 Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system (CNS). The current treatment protocol for glioblastoma patients is surgery and radiation therapy followed by treatment with temozolomide. Despite the development of multimodal treatment, the median life expectancy for patients with GBM is still approximately 14 months, and fewer than 5% of patients survive beyond 5 years of diagnosis 1. Unlike other malignant solid cancers, glioblastoma cells prefer to invade diffusely rather than create systemic metastases. The aggressive feature of glioblastoma cells is their invasion of surrounding normal brain tissues, which is the primary reason for incomplete surgical resection, chemo-radiation resistance and inevitable recurrence. There are very limited possibilities to target these processes therapeutically 2. In light of the poor outcome from current therapies in glioblastoma patients, a better understanding of GBM invasion may provide more effective interventions to manage this devastating disease.

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Section: Discussionmentioning

confidence: 99%

TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions

Yang

et al. 2020

Sci Rep

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“…Chronic pain in patients with OA primarily depends on the activation of sensory neurons innervating the affected joint 30 . Some evidence has shown that TLR4 on small-diameter, somatosensory neurons is directly involved in pain conduction and regulation 31 . In addition, pain in arthritic animal models was shown to be closely related to TLR4 signaling pathways 32 .…”

Section: Discussionmentioning

confidence: 99%

TAP2, a peptide antagonist of Toll-like receptor 4, attenuates pain and cartilage degradation in a monoiodoacetate-induced arthritis rat model

Park

Hong

Yin

et al. 2020

Sci Rep

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Because inflammation in osteoarthritis (OA) is related to the Toll-like receptor 4 (TLR4) signaling cascades, TLR4 is a reasonable target for developing therapeutics for OA. Thus, we investigated whether TAP2, a peptide antagonist of TLR4, reduces the monoiodoacetate (MIA)-induced arthritic pain and cartilage degradation in rats. TLR4 expression of human OA chondrocytes and synoviocytes and the knee joint tissue of MIA-induced arthritis were evaluated. MIA-induced arthritic model using Sprague–Dawley rats (6 week-old-male) were treated with TAP2, a TLR4 antagonist, and evaluated with behavioral test, immunohistochemistry, and quantitative PCR. TLR4 was highly expressed in the knee joints of patients with OA and the MIA-induced rat model. Further, a single intraarticular injection of TAP2 (25 nmol/rat) molecules targeting TLR4 on day 7 after MIA injection dramatically attenuated pain behavior for about 3 weeks and reduced cartilage loss in the knee joints and microglial activation in the spinal dorsal horns. Likewise, the mRNA levels of TNFα and IL-1β, reactive oxygen species, and the expression of MMP13 in the knee joints of TAP2-treated rats was significantly decreased by TAP2 treatment compared with the control. Moreover, interestingly, the duration of OA pain relief by TAP2 was much longer than that of chemical TLR4 antagonists, such as C34 and M62812. In conclusion, TAP2 could effectively attenuate MIA-induced arthritis in rats by blocking TLR4 and its successive inflammatory cytokines and MMP13. Therefore, TAP2 could be a prospective therapeutic to treat patients with OA.

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“…The MHWTs were measured up to 60 min before HC067047 administration and every 30 min after its administration on day 3 following IONI as described above. The administered tranilast and HC067047 doses were based on previous reports [14,44].…”

Section: Drug Administrationmentioning

confidence: 99%

Increase in IGF-1 Expression in the Injured Infraorbital Nerve and Possible Implications for Orofacial Neuropathic Pain

Sugawara

Shinoda

Hayashi

et al. 2019

IJMS

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Insulin-like growth factor-1 (IGF-1) is upregulated in the injured peripheral nerve bundle and controls nociceptive neuronal excitability associated with peripheral nerve injury. Here, we examined the involvement of IGF-1 signaling in orofacial neuropathic pain following infraorbital nerve injury (IONI) in rats. IONI promoted macrophage accumulation in the injured ION, as well as in the ipsilateral trigeminal ganglion (TG), and induced mechanical allodynia of the whisker pad skin together with the enhancement of neuronal activities in the subnucleus caudalis of the spinal trigeminal nucleus and in the upper cervical spinal cord. The levels of IGF-1 released by infiltrating macrophages into the injured ION and the TG were significantly increased. The IONI-induced the number of transient receptor potential vanilloid (TRPV) subfamily type 4 (TRPV4) upregulation in TRPV subfamily type 2 (TRPV2)-positive small-sized, and medium-sized TG neurons were inhibited by peripheral TRPV2 antagonism. Furthermore, the IONI-induced mechanical allodynia was suppressed by TRPV4 antagonism in the whisker pad skin. These results suggest that IGF-1 released by macrophages accumulating in the injured ION binds to TRPV2, which increases TRPV4 expression in TG neurons innervating the whisker pad skin, ultimately resulting in mechanical allodynia of the whisker pad skin.

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Expression profiles of TRPV1, TRPV4, TLR4 and ERK1/2 in the dorsal root ganglionic neurons of a cancer-induced neuropathy rat model

Cited by 20 publications

References 53 publications

TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions

TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions

TAP2, a peptide antagonist of Toll-like receptor 4, attenuates pain and cartilage degradation in a monoiodoacetate-induced arthritis rat model

Increase in IGF-1 Expression in the Injured Infraorbital Nerve and Possible Implications for Orofacial Neuropathic Pain

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