RGS proteins as targets in the treatment of intestinal inflammation and visceral pain: New insights and future perspectives

Sałaga, Maciej; Storr, Martin; Martemyanov, Kirill A.; Fichna, Jakub

doi:10.1002/bies.201500118

Cited by 16 publications

(18 citation statements)

References 93 publications

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“…Interestingly, oxidative stress conditions increase RGS2 mRNA levels [79,80]; moreover, RGS2 contributes to the regulation of some enzymes involved in antioxidant defense, namely glyoxalase-1 and glutathione reductase-1 [81]. Finally, RGS2 has been shown to be involved in the pathophysiology of gastrointestinal inflammation and visceral pain, mostly regulating T-cell immunity [79,82,83]. In our opinion, the observed RGS2 gene downregulation can be viewed as the consequence of an indirect positive effect of GP on the overall cattle gastrointestinal tract homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Nutrigenomic Effects of Long-Term Grape Pomace Supplementation in Dairy Cows

Pauletto

Elgendy

Ianni

et al. 2020

Animals

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The increasing demand for more animal products put pressure on improving livestock production efficiency and sustainability. In this context, advanced animal nutrition studies appear indispensable. Here, the effect of grape pomace (GP), the polyphenol-rich agricultural by-product, was evaluated on Holstein-Friesian cows’ whole-blood transcriptome, milk production and composition. Two experimental groups were set up. The first one received a basal diet and served as a control, while the second one received a 7.5% GP-supplemented diet for a total of 60 days. Milk production and composition were not different between the group; however, the transcriptome analysis revealed a total of 40 genes significantly affected by GP supplementation. Among the most interesting down-regulated genes, we found the DnaJ heat-shock protein family member A1 (DNAJA1), the mitochondrial fission factor (MFF), and the impact RWD domain protein (IMPACT) genes. The gene set enrichment analysis evidenced the positive enrichment of ‘interferon alpha (IFN-α) and IFN-γ response’, ‘IL6-JAK-STAT3 signaling’ and ‘complement’ genes. Moreover, the functional analysis denoted positive enrichment of the ‘response to protozoan’ and ‘negative regulation of viral genome replication’ biological processes. Our data provide an overall view of the blood transcriptomic signature after a 60-day GP supplementation in dairy cows which mainly reflects a GP-induced immunomodulatory effect.

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Section: Discussionmentioning

confidence: 99%

Nutrigenomic Effects of Long-Term Grape Pomace Supplementation in Dairy Cows

Pauletto

Elgendy

Ianni

et al. 2020

Animals

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“…For example, upregulation of miR-29a in the blood exosomes of IBS patients is involved in the regulation of intestinal permeability [15]. Regulators of G protein signaling (RGS) proteins play a role in gastrointestinal inflammation and visceral pain by regulating the G protein-coupled receptors (GPCRs) in the gastrointestinal tract, thereby modulating the activity of endogenous opioid, cannabinoid, and serotonin systems [16]. Moreover, a recent study reports that mesenchymal stem cell-derived exosomal miR-148b-5p mediates the immunosuppressive effect through downregulating 15-LOX-1 in macrophages in inflammatory bowel disease [17].…”

Section: Introductionmentioning

confidence: 99%

Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells

Xing

Xue

et al. 2021

Gastroenterology Research and Practice

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Aim. Irritable bowel syndrome (IBS) is a multifactorial functional bowel disorder characterized by disruption of the intestinal barrier. Circulating exosomal microRNAs (miRNAs) are involved in regulating epithelial barrier function, and upregulation of miR-148b-5p has been detected in IBS. However, whether exosomal miR-148-5p is involved in the IBS pathogenesis remains unclear. This study was aimed at investigating the relationship of exosomal miR-148-5p with colonic epithelial permeability. Methods. Exosomes were isolated from the serum of IBS patients and healthy controls. HT-29 cells were cultured with the IBS-derived serum exosomes (IBS-exo). Exosome uptake assay was used to evaluate whether the IBS-exo could be absorbed by HT-29 cells. FITC-Dextran flux and transepithelial/endothelial electrical resistance were measured to evaluate epithelial permeability. A luciferase reporter assay was used to determine whether the regulator of G protein signaling- (RGS-) 2 is a target gene of miR-148b-5p. Results. miR-148b-5p was obviously elevated in the IBS-exo compared to the control-exo. Upregulation of miR-148b-5p was observed in the HT-29 cells cultured with IBS-exo. Exposure to IBS-exo increased cell permeability and decreased RGS2 expression. The IBS-exo-induced alterations were obviously reversed by interfering with the miR-148b-5p expression. Mimicking the IBS-exo treatment, miR-148b-5p overexpression increased cell permeability and downregulated RGS2 expression, which were abrogated by overexpressing RGS2. The luciferase reporter assay revealed that RGS2 was a direct target of miR-148b-5p. Conclusions. Serum-derived exosomes from IBS patients increase colonic epithelial permeability via miR-148b-5p/RGS2 signaling.

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“…RGS proteins act as GTPase-activating proteins (GAPs) by interacting directly with activated Gα and accelerating GTP hydrolysis thereby promoting G-protein inactivation upon reassembly of the inactive Gαβγ heterotrimer. The action of the RGS proteins is essential in providing control over both the extent and duration of signaling (Hollinger and Hepler, 2002; Ross and Wilkie, 2000) and deficits in this control results in severe dysregulation of GPCR signaling causing a number of human pathophysiological conditions (Woodard et al, 2015; Salaga et al, 2016; Druey, 2017; Sjögren, 2017).…”

Section: Introductionmentioning

confidence: 99%

Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex

Patil

Rangarajan

Novick

et al. 2018

eLife

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Signaling by the G-protein-coupled receptors (GPCRs) plays fundamental role in a vast number of essential physiological functions. Precise control of GPCR signaling requires action of regulators of G protein signaling (RGS) proteins that deactivate heterotrimeric G proteins. RGS proteins are elaborately regulated and comprise multiple domains and subunits, yet structural organization of these assemblies is poorly understood. Here, we report a crystal structure and dynamics analyses of the multisubunit complex of RGS7, a major regulator of neuronal signaling with key roles in controlling a number of drug target GPCRs and links to neuropsychiatric disease, metabolism, and cancer. The crystal structure in combination with molecular dynamics and mass spectrometry analyses reveals unique organizational features of the complex and long-range conformational changes imposed by its constituent subunits during allosteric modulation. Notably, several intermolecular interfaces in the complex work in synergy to provide coordinated modulation of this key GPCR regulator.

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RGS proteins as targets in the treatment of intestinal inflammation and visceral pain: New insights and future perspectives

Cited by 16 publications

References 93 publications

Nutrigenomic Effects of Long-Term Grape Pomace Supplementation in Dairy Cows

Nutrigenomic Effects of Long-Term Grape Pomace Supplementation in Dairy Cows

Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells

Structural organization of a major neuronal G protein regulator, the RGS7-Gβ5-R7BP complex

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