TRPV4 inhibitor HC067047 produces antidepressant-like effect in LPS-induced depression mouse model

Li, Wei; Yang, Xu; Liu, Zhenghai; Shi, Mei; Zhang, Yuan; Deng, Yi; Zhong, Xiaolin; Chen, Ling; He, Jie; Zeng, Jiayu; Luo, Mingying; Cao, Wenzhi; Wan, Wei Keat

doi:10.1016/j.neuropharm.2021.108834

Cited by 27 publications

(19 citation statements)

References 38 publications

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“…Lipopolysaccharide (LPS) can activate microglia to cause depressive symptoms, whose severity is connected with the level of inflammatory cytokines [107,108]. LPS also induces depression by activating microglia, and many drugs have exerted an antidepression effect by inhibiting the activation of LPS-induced microglia [109][110][111]. O'Connor et al revealed a pivotal role for interferon-γ and tumor necrosis factor-α in inducing indoleamine 2,3-dioxygenase and depressive-like symptoms in response to bacillus Calmette-Guerin [112].…”

Section: Microsphere Embolism Modelmentioning

confidence: 99%

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

Xia

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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Poststroke depression (PSD) does not exist before and occurs after the stroke. PSD can appear shortly after the onset of stroke or be observed in the weeks and months after the acute or subacute phase of stroke. The pathogenesis of PSD is unclear, resulting in poor treatment effects. With research advancement, immunoactive cells in the central nervous system, particularly microglia, play a role in the occurrence and development of PSD. Microglia affects the homeostasis of the central nervous system through various factors, leading to the occurrence of depression. The research progress of microglia in PSD has been summarized to review the evidence regarding the pathogenesis and treatment target of PSD in the future.

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Section: Microsphere Embolism Modelmentioning

confidence: 99%

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

Xia

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…The TRPV4 in airway epithelial cells and macrophages can be activated by LPS stimulation, which triggered downstream protective responses and anti-inflammatory pathways [ 13 , 14 ]. Moreover, TRPV4 could protect lung from injury upon intratracheal Pseudomonas aeruginosa in mice through a novel mechanism of molecular switching of LPS signaling [46] , and there was a significant increase in TRPV4 in the hippocampus of a depression mouse model induced by LPS [47] . These results indicated that Cg TRPV4 might share a similar role in sensing both biotic and abiotic stresses with their homologues in other species.…”

Section: Discussionmentioning

confidence: 97%

The expression profile of a multi-stress inducible transient receptor potential vanilloid 4 (TRPV4) in Pacific oyster Crassostrea gigas

Yang

Jiang

et al. 2022

Fish and Shellfish Immunology Reports

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“…Furthermore, in a model of TMAO (choline-metabolized trimethylamine N-oxide)-induced M1 polarization, both inhibiting NLRP3 and deleting the NLRP3 gene in macrophages resulted in a lower profile of M1 signature expression ( Il-1 , Il-6 , Cxcl10 , Tnf-α ), demonstrating that NLRP3 activation is important for M1 macrophage polarization [ 28 ]. Of note, in the LPS-induced depression mouse model, the TRPV4 inhibitor HC067047 or TRPV4 shRNA could effectively rescue the abnormal behaviors by decreasing the expression of the NLRP3 [ 9 ]. However, the involvement of NLRP3 in M1 synovial macrophage polarization in OA remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria-derived ROS were shown to be elevated in LPS-treated macrophages, which was associated with both NLRP3 activation and M1 macrophage polarization [ 9 ]. The latest research demonstrated that aerobic glycolysis was induced upon activation and the activities of the respiratory chain (oxidative phosphorylation) were attenuated in M1 macrophage, allowing for reactive oxygen species (ROS) production [ 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…TRPV4 (transient receptor potential vanilloid 4), as a nonselective polymodal cation channel, is triggered by numerous stimuli (such as mechanical, temperature, and hypo-osmolarity) and can be blocked by pharmacological inhibitors [ 8 , 9 ]. The effect of TRPV4 on mechanical stimulation has been widely investigated in different diseases [ 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway

Sun

et al. 2022

Antioxidants

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Osteoarthritis (OA) is a low-level inflammatory disease in which synovial macrophage M1 polarization exacerbates the progression of synovitis and OA. Notedly, the ROS (reactive oxygen species) level in macrophages is intimately implicated in macrophage M1 polarization. TRPV4 (transient receptor potential channel subfamily V member 4), as an ion channel, plays a pivotal role in oxidative stress and inflammation. In this study, we investigated the role of TRPV4 in OA progression and M1 macrophage polarization. Male adult Sprague–Dawley (SD) rats underwent a medial meniscus radial transection operation to create an OA model in vivo and RAW 264.7 cells were intervened with 100 ng/mL LPS (lipopolysaccharide) to induce M1-polarized macrophages in vitro. We demonstrated that the infiltration of M1 synovial macrophages and the expression of TRPV4 were increased significantly in OA synovium. In addition, intra-articular injection of HC067074 (a specific inhibitor of TRPV4) alleviated the progression of rat OA and significantly decreased synovial macrophage M1 polarization. Further mechanisms suggested that ROS production by M1 macrophages was decreased after TRPV4 inhibition. In addition, NLRP3 (pyrin domain containing protein 3) as a downstream effector of ROS in M1-polarized macrophage, was significantly suppressed following TRPV4 inhibition. In conclusion, this study discovered that inhibition of TRPV4 delays OA progression by inhibiting M1 synovial macrophage polarization through the ROS/NLRP3 pathway.

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TRPV4 inhibitor HC067047 produces antidepressant-like effect in LPS-induced depression mouse model

Cited by 27 publications

References 38 publications

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

The expression profile of a multi-stress inducible transient receptor potential vanilloid 4 (TRPV4) in Pacific oyster Crassostrea gigas

Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway

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