Similar Datasets
Project description:Enteric Glia treated with exATP
2020-11-15 | GSE134941 | GEO
Project description:IL-1 signaling in enteric glia initiates acute intestinal inflamation and modulates postoperative motility disturbances by triggering a reactive glial phenotype named enteric gliosis. Enteric glia modulate macrophage function and activity in this reactive state by releasing a unique panel of chemokines and cytokines. An enteric glia-selective knockout of this pathway ameliorates acute postoperative inflammation and prevents postoperative ileus.
2022-07-11 | GSE205610 | GEO
Project description:BACKGROUND Enteric glia contribute to the pathophysiology of various intestinal immune-driven diseases, such as postoperative ileus (POI), a motility disorder and common complication after abdominal surgery. Enteric gliosis of the intestinal muscularis externa (ME) has been identified as part of POI development. However, the glia-restricted responses and activation mechanisms are poorly understood. The sympathetic nervous system becomes rapidly activated by abdominal surgery. It modulates intestinal immunity, innervates all intestinal layers, and directly interfaces with enteric glia. We hypothesized that sympathetic innervation controls enteric glia reactivity in response to surgical trauma. METHODS Sox10iCreERT2/Rpl22HA/+ mice were subjected to a mouse model of laparotomy or intestinal manipulation to induce POI. Histological, protein, and transcriptomic analyses were performed to analyze glia-specific responses. Interactions between the sympathetic nervous system and enteric glia were studied in mice chemically depleted of TH+ sympathetic neurons and glial-restricted Sox10iCreERT2/JellyOPfl/+/Rpl22HA/+ mice, allowing optogenetic stimulation of β-adrenergic downstream signaling and glial-specific transcriptome analyses. A laparotomy model was used to study the effect of sympathetic signaling on enteric glia in the absence of intestinal manipulation. Mechanistic studies included adrenergic receptor expression profiling in vivo and in vitro and adrenergic agonism treatments of primary enteric glial cell cultures to elucidate the role of sympathetic signaling in acute enteric gliosis and POI. RESULTS With ~4000 differentially expressed genes, the most substantial enteric glia response occurs early after intestinal manipulation. During POI, enteric glia switch into a reactive state and continuously shape their microenvironment by releasing inflammatory and migratory factors. Sympathetic denervation reduced the inflammatory response of enteric glia in the early postoperative phase. Optogenetic and pharmacological stimulation of β-adrenergic downstream signaling triggered enteric glia reactivity. Finally, distinct adrenergic agonists revealed β-1/2 adrenoceptors as the molecular targets of sympathetic–driven enteric glial reactivity. CONCLUSIONS Enteric glia act as early responders during post-traumatic intestinal injury and inflammation. Intact sympathetic innervation and active β-adrenergic receptor signaling in enteric glia is a trigger of the immediate glial postoperative inflammatory response. With immune-activating cues originating from the sympathetic nervous system as early as the initial surgical incision, adrenergic signaling in enteric glia presents a promising target for preventing POI development.
2023-11-15 | GSE198889 | GEO
Project description:Purinergic signaling in enteric gliosis [Dataset EV2]
| PRJNA556860 | ENA
Project description:Purinergic signaling in enteric gliosis [Dataset EV1]
| PRJNA556859 | ENA
Project description:Enteric glial cells (EGC) modulate motility, maintain gut homeostasis, and contribute to neuroinflammation in intestinal diseases and motility disorders. Damage induces a reactive glial phenotype known as "gliosis", but the molecular identity of the inducing mechanism and triggers of "enteric gliosis" are poorly understood. We tested the hypothesis that surgical trauma during intestinal surgery triggers ATP release that drives enteric gliosis and inflammation leading to impaired motility in postoperative ileus (POI). ATP activation of a p38-dependent MAPK pathway triggers cytokine release and a gliosis phenotype in murine (and human) EGCs. Receptor antagonism and genetic depletion studies revealed P2X2 as the relevant ATP receptor and pharmacological screenings identified ambroxol as a novel P2X2 antagonist. Ambroxol prevented ATP-induced enteric gliosis, inflammation, and protected against dysmotility, while abrogating enteric gliosis in human intestine exposed to surgical trauma. We identified a novel pathogenic P2X2-dependent pathway of ATP-induced enteric gliosis, inflammation and dysmotility in humans and mice. Interventions that block enteric glial P2X2 receptors during trauma may represent a novel therapy in treating POI and immune-driven intestinal motility disorders.
| S-EPMC7799361 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-11-15 | GSE134943 | GEO
Project description:surgery samples of patients at early and late timepoints of a pancreatectomy
2020-11-15 | GSE149181 | GEO
Project description:Background: Current studies provide compelling evidence that the enteric nervous system and neighboring resident macrophages in the muscularis externa modulate neuroimmune processes in the gut after abdominal surgery. While substantial knowledge exists about macrophage-enteric glia interactions, the fate of enteric neurons, which have an indispensable role in gut homeostasis and gastrointestinal motility, has not been thoroughly investigated during enteric neuroinflammation. Therefore, we investigated the impact of enteric neuron-macrophage interactions on postoperative trauma and subsequent motility disturbances, i.e., postoperative ileus. Methods: Neuroinflammation and postoperative ileus were induced in various transgenic mice by surgical manipulation of the small intestine. We studied enteric neurons and macrophage-specific transcriptomes using bulk RNA-Seq in neuron-specific RiboTag mice and sorted CX3CR1-GFP+ macrophages. To investigate their intercellular communication, we treated CX3CR1-GFP+ mice with CSFR1-antibody to deplete macrophages and subsequently induce POI through surgical trauma. These mice were examined for gastrointestinal motility, immune cell infiltration, and neuronal function. Ultimately, we validated the murine data in human gut samples collected early and late during abdominal surgery to understand the impact of surgical manipulation on patients' enteric nervous system function. Results: We detected strong neuronal activation in the early postsurgical phase, followed, after 24h, by transcriptional signatures of neuronal proliferation, neuronal death, and synaptic degradation. Neuron-specific transcriptome analysis confirmed these changes and verified the neuronal responses to the inflammatory environment. Simultaneously, our study revealed a neurodegenerative profile in macrophage-specific transcriptomes during POI. Depletion of macrophages before surgical manipulation led to decreased neuronal death, less synaptic decay, and improved GI motility, emphasizing the essential role of macrophages in neurodegeneration during intestinal neuroinflammation. In human jejunal muscularis externa samples, taken at early and late stages of pancreatectomies, we detected reactive and dying neurons with dysregulated gene expression of synaptic signaling and neurogenic processes. Conclusion: Surgical trauma and acute intestinal inflammation activate enteric neurons and induce neurodegeneration with severe synaptic decay, predominantly mediated by resident macrophages. Future studies should focus on neuroprotective mechanisms to dampen neurodegeneration and promote faster recovery from postoperative inflammation and motility disturbances.
2024-12-31 | GSE263125 | GEO
Project description: Not available
| S-EPMC10631040 | biostudies-literature