Expression and functional characterization of transient receptor potential vanilloid 4 in the dorsal root ganglion and spinal cord of diabetic rats with mechanical allodynia

Cui, Yuanyuan; Li, Mengying; Li, Yuting; Ning, Jiayi; Gou, Xin; Shi, Juan; Li, Yunqing

doi:10.1016/j.brainresbull.2020.05.010

Cited by 8 publications

(6 citation statements)

References 42 publications

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“…Earlier studies have demonstrated that TRPV4 is highly expressed in DRG neurons of rats (Cao et al., 2009; Cui et al., 2020) and mice (Girard et al., 2013). However, whether the DRG neurons expressing TRPV4 innervate skeletal muscle afferents has not been evaluated previously.…”

Section: Discussionmentioning

confidence: 98%

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Antagonism of TRPV4 channels partially reduces mechanotransduction in rat skeletal muscle afferents

Fukazawa

Hori

Hotta

et al. 2023

The Journal of Physiology

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Section: Discussionmentioning

confidence: 98%

“…J Physiol 601.8 Cui et al, 2020) and mice (Girard et al, 2013). However, whether the DRG neurons expressing TRPV4 innervate skeletal muscle afferents has not been evaluated previously.…”

Section: Controlmentioning

confidence: 99%

Antagonism of TRPV4 channels partially reduces mechanotransduction in rat skeletal muscle afferents

Fukazawa

Hori

Hotta

et al. 2023

The Journal of Physiology

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“…TRPV4, a member of the transient receptor potential ion channel receptor family [ 19 ], is crucial for many physiological processes, particularly the operation of the sensory system [ 21 ]. Different stimuli, such as osmotic pressure changes and mechanical, chemical, and thermal stimuli, could open the TRPV4 channels [ 21 , 22 , 23 ]. Additionally, TRPV4 has been implicated in mediating mechanical and hypotonic hyperalgesia in neuropathic pain model-induced pain [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…According to experimental studies, TRPV4 controls mechanical and thermal hyperalgesia in neuropathic pain [ 21 , 22 ]. TRPV4 inhibition partially reverses the mechanical pain after sustained compression of the dorsal root ganglion in rats [ 23 ]. Since the rapid proliferation of cancer cells severely squeezes the bone marrow cavity, which causes changes in cell surface pressure, and TRPV4 could sense changes in cell surface mechanical and osmotic pressure [ 24 ], we chose to study TRPV4 in the TRPV family.…”

Section: Introductionmentioning

confidence: 99%

TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats

Niu

Liu

et al. 2023

Brain Sciences

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Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4–6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4–6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4–6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4–6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain.

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“…Transient receptor potential (TRP) channel TRPV4 is a non-selective cation channel that is ubiquitously expressed in most tissues, including bone, skin, vasculature, heart, brain, lungs, liver, kidneys, and bladder 1 – 3 . The channel is activated by warm temperatures (>27 °C) 4 , an increase of cell volume, endogenous ligands such as derivatives of arachidonic acid, and synthetic compounds 5 – 7 .…”

Section: Introductionmentioning

confidence: 99%

Structure of human TRPV4 in complex with GTPase RhoA

et al. 2023

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Transient receptor potential (TRP) channel TRPV4 is a polymodal cellular sensor that responds to moderate heat, cell swelling, shear stress, and small-molecule ligands. It is involved in thermogenesis, regulation of vascular tone, bone homeostasis, renal and pulmonary functions. TRPV4 is implicated in neuromuscular and skeletal disorders, pulmonary edema, and cancers, and represents an important drug target. The cytoskeletal remodeling GTPase RhoA has been shown to suppress TRPV4 activity. Here, we present a structure of the human TRPV4-RhoA complex that shows RhoA interaction with the membrane-facing surface of the TRPV4 ankyrin repeat domains. The contact interface reveals residues that are mutated in neuropathies, providing an insight into the disease pathogenesis. We also identify the binding sites of the TRPV4 agonist 4α-PDD and the inhibitor HC-067047 at the base of the S1-S4 bundle, and show that agonist binding leads to pore opening, while channel inhibition involves a π-to-α transition in the pore-forming helix S6. Our structures elucidate the interaction interface between hTRPV4 and RhoA, as well as residues at this interface that are involved in TRPV4 disease-causing mutations. They shed light on TRPV4 activation and inhibition and provide a template for the design of future therapeutics for treatment of TRPV4-related diseases.

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Expression and functional characterization of transient receptor potential vanilloid 4 in the dorsal root ganglion and spinal cord of diabetic rats with mechanical allodynia

Cited by 8 publications

References 42 publications

Antagonism of TRPV4 channels partially reduces mechanotransduction in rat skeletal muscle afferents

Antagonism of TRPV4 channels partially reduces mechanotransduction in rat skeletal muscle afferents

TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats

Structure of human TRPV4 in complex with GTPase RhoA

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