Inhibition of TRPV4 rescues impaired excitability and social deficits in NAc-specific Shank3-deficient mice.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139683 | GEO | 2022/10/01
REPOSITORIES: GEO
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Project description:Background: Depression is the leading cause of disability which produces enormous health and economic burdens. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activities of D1- or D2-type medium spiny neurons (MSNs). Methods: To separate D1- or D2-MSN specific transcriptomes in the NAc, RiboTag (RT) mice were crossed with D1- or D2-Cre lines and subjected to chronic social defeat stress. The cell-type specifically tagged ribosome-mRNA complex was pulled down by anti-HA antibody, and purified RNAs were subjected to RNA sequencing. Sequencing data were analyzed and defined differentially expressed genes (DEGs) were validated with RNAscope and viral overexpression in vivo. Results: Both MSN subtypes express distinct gene expression profiles according to stress groups. The DEGs are correlated with depression relevant gene ontology terms. Behavioral susceptibility and resilience are also correlated with subsets of DEGs, especially in D1-MSNs. Conclusions: Distinct subsets of genes are modulated in a cell-type specific manner in the NAc of depressed mice. Here we provided valuable transcriptome data sets for future studies on depression.
2021-07-09 | GSE147640 | GEO
Project description:Comparing gene expression profile in 3T3-F442A adipocytes with shRNA against TRPV4 or GFP. TRPV4 is an ion channel expressed in adipocytes. Results provided information that how loss-of-function of TRPV4 affects gene expression in adipocytes. 4 samples were analyzed as two groups: shGFP (control) and shTRPV4 (experimental). Each group has two replicates.
2012-10-12 | E-GEOD-40280 | biostudies-arrayexpress
Project description:Abstract Background Chronic constipation is prevalent and involves both colon sensitivity and various changes in intestinal bacteria, particularly mucosa-associated microflora. Here we examined regulatory mechanisms of TRPV4 expression by co-culturing colon epithelial cell lines with intestinal bacteria and their derivatives. We also investigated TRPV4 expression in colon epithelium from patients with constipation. Methods Colon epithelial cell lines were co-cultured with various enterobacteria (bacterial components and supernatant), folate, LPS, or short chain fatty acids (SCFAs). TRPV4 expression levels and promoter DNA methylation were assessed using pyrosequencing, and microarray network analysis. For human samples, correlation coefficients were calculated and multiple regression analyses were used to examine the association between clinical background, rectal TRPV4 expression level and mucosa-associated microbiota. Results Co-culture of CCD841 cells with P. acnes, C. perfringens, or S. aureus transiently decreased TRPV4 expression but did not induce methylation. Co-culture with clinical isolates and standard strains of K. oxytoca, E. faecalis, or E. coli increased TRPV4 expression in CCD841 cells, and TRPV4 and TNF-alpha expression were increased by E. coli culture supernatants but not bacterial components. Although folate, LPS, IL-6, TNF-alpha, or SCFAs alone did not alter TRPV4 expression, TRPV4 expression following exposure to E. coli culture supernatants was inhibited by butyric acid or TNF-alphaR1 inhibitor and increased by p38 inhibitor. Microarray network analysis showed activation of TNF-alpha, cytokines, and NOD signaling. TRPV4 expression was higher in constipated patients from the terminal ileum to the colorectum, and multiple regression analyses showed that low stool frequency, frequency of defecation aids, and duration were associated with TRPV4 expression. Meanwhile, incomplete defecation, time required to defecate, and number of defecation failures per 24 hours were associated with increased E. faecalis frequency. Conclusions Colon epithelium cells had increased TRPV4 expression upon co-culture with K. oxytoca, E. faecalis, or E. coli supernatants, as well as TNFα-stimulated TNFαR1 expression via a pathway other than p38. Butyrate treatment suppressed this increase. Epithelial TRPV4 expression was increased in constipated patients, suggesting that TRPV4 together with increased frequency of E. faecalis may be involved in the pathogenesis of various constipation symptoms.
2022-07-15 | GSE208164 | GEO
Project description:Comparing gene expression profile in 3T3-F442A adipocytes with shRNA against TRPV4 or GFP. TRPV4 is an ion channel expressed in adipocytes. Results provided information that how loss-of-function of TRPV4 affects gene expression in adipocytes.
2012-10-12 | GSE40280 | GEO
Project description:RNA-seq of TC28a2 cells following TRPV4 activation/inhibition in the presence and absence of prior TGFβ3 stimulation. The experiment was performed to determine the effect of TRPV4 activity on gene expression in the presence and absence of TGFβ stimulation. TGFβ3 was used to stimulate TGFβ signalling, GSK1016790A (GSK101) was used to activate TRPV4, GSK2193874 (GSK219) was used to inhibit TRPV4 and DMSO was used as a vehicle control.
2022-01-17 | E-MTAB-10279 | biostudies-arrayexpress
Project description:MicroRNA regulates protein expression of cells by repressing translation of specific target messenger transcripts. Loss of the neuron specific microRNA miR-128 in Dopamine D1-receptor expressing neurons in the murine striatum (D1-MSNs) lead to increased neuronal excitability, locomotor hyperactivity and fatal epilepsy. To examine expression changes in the absence of miR-128 in D1-MSNs, we used mice expressing EGFP-tagged ribosomes in D1-MSNs with either D1-MSN-specific homozygous deletion of miR-128-2 locus or no deletion. Transcripts co-immunoprecipitated with tagged ribosomes were analyzed by microarray. 9 mutant animals ( D1-MSN-tagged ribosome; D1-MSN specific miR-128-2 homozygous deletion) and 7 age matched littermate control animals (D1-MSN-tagged ribosome only).
2014-01-07 | E-GEOD-48813 | biostudies-arrayexpress
Project description:TRPV4 is a cell surface-expressed calcium-permeable cation channel that mediates cell-specific effects on cellular morphology and function. Dominant missense mutations of TRPV4 cause various forms of inherited neuropathy, but the pathogenic mechanisms are unknown. Using an unbiased screen, we sought to identify novel TRPV4 interactors that may be relevant to disease pathogenesis.
2021-01-29 | PXD023758 | Pride
Project description:The functional complexity of nucleus accumbens (NAc) has been extensively characterized in recent years. However, the molecular and cellular heterogeneity beyond the established D1 and D2 medium spiny neuron (MSN) subtypes, which likely underlie its diverse functions, are not well understand. Here, we present the cell taxonomy of mouse NAc generated from single-cell transcriptomic profiling, which not only reveals a rich cellular heterogeneity within both NAc MSN and interneuron populations, but also identified tight correlation between the transcriptional feature and spatial distribution of NAc neuron subtypes, supporting the notion that functional heterogeneity of NAc sub-regions can arises from differential distribution of molecularly distinct neuronal populations. To further test this idea, we focused on a D1 MSN subtype identified from our analysis and demonstrated that these cells possess distinct anatomic location, neural connection and more importantly, behavioral function. Collectively, our work not only created comprehensive cell taxonomy of NAc, but also provided insights into how functional heterogeneity is embedded in this brain region.
2021-08-24 | GSE118020 | GEO
Project description:Epigenetic modifications, including the role of miRs in various diseases, are key regulators of gene expression. In this study we aimed to explore whether epigenetic alterations could play a role in the TRPV4-mediated regulation of miR-146a. Here we report that there is no significant differences in the methylation status of the examined 10 CpG sites on miR146a promoter between WT and TRPV4 KO cells under LPS treatment, indicating that the regulation of miR-146a by TRPV4 may not be mediated by methylation changes at these specific sites.
2024-10-23 | GSE271253 | GEO
Project description:The mechanosensitive ion channels Transient Receptor Potential Vanilloid 4 (TRPV4) and PIEZO1 transduce physiologic and supraphysiologic magnitudes of mechanical signals in the chondrocyte, respectively. TRPV4 activation promotes chondrogenesis, while PIEZO1 activation by supraphysiologic deformations drives cell death. The mechanisms by which activation of these channels discretely drives changes in gene expression to alter cell behavior remains to be determined. To date, no studies have contrasted the transcriptomic response to activation of these channels, nor has any published data attempted to correlate these transcriptomes to alterations in cellular function. This study used RNA sequencing to comprehensively investigate the transcriptomes associated with activation of TRPV4 or PIEZO1, revealing that TRPV4 and PIEZO drive distinct transcriptomes, but also exhibit unique co-regulated clusters of genes. Notably, activation of PIEZO1 through supraphysiologic deformation induced a transient inflammatory profile that overlapped with the interleukin (IL)-1-responsive transcriptome and contained genes associated with cartilage degradation and osteoarthritis progression. However, both TRPV4 and PIEZO1 were also shown to elicit anabolic effects. PIEZO1 expression promoted a pro-chondrogenic transcriptome under unloaded conditions, and daily treatment with PIEZO1 agonist Yoda1 significantly increased sulfated glycosaminoglycan deposition in vitro. These findings emphasize the presence of a broad “mechanome” with distinct effects of TRPV4 and PIEZO1 activation in chondrocytes, suggesting complex roles for PIEZO1 in both the physiologic and pathologic responses of chondrocytes. The identification of transcriptomic profiles unique to or shared by PIEZO1 and TRPV4 (distinct from IL-1-induced inflammation) could inform future therapeutic designs targeting these channels for the management and treatment of osteoarthritis.
2024-06-05 | GSE269159 | GEO