Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis

Hutter, Senta; Haaften, Wouter T. van; Hünerwadel, A.; Baebler, Katharina; Herfarth, Neel; Raselli, Tina; Mamie, Céline; Misselwitz, Benjamin; Rogler, Gerhard; Weder, Bruce; Dijkstra, Gerard; Meier, Claus; Vallière, Cheryl de; Weber, Achim; Silva, Pedro Henrique Imenez; Wagner, Carsten A.; Frey-Wagner, Isabelle; Ruiz, Pedro A.; Hausmann, Martin

doi:10.1093/ecco-jcc/jjy118

Cited by 35 publications

(50 citation statements)

References 61 publications

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“…In fact, this could be noticed already at the level of generic EMT in Eq. (8) where the trace of the expression in the brackets is equal identically to zero such that only the last term contributes to the EMT trace.…”

Section: Effective Ym Theory and The Mirror Symmetrymentioning

confidence: 99%

“…[6] and references therein. For confined QCD, with SU(3) color gauge symmetry, there is a rather unique contribution to the ground state energy of the Universe that emerges from the non-perturbative quantum-topological fluctuations of the quark and gluon fields [1,[7][8][9], namely, QCD top −(5 ± 1) × 10 9 MeV 4 . Given the fact that the CC term observed in astrophysical measurements is very small (and positive), CC 3 × 10 −35 MeV 4 , to the first approximation one must exclude the negative-valued topological vacuum contribution with an accuracy of a few tens of decimal digits.…”

Section: Introductionmentioning

confidence: 99%

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Mirror symmetry of quantum Yang–Mills vacua and cosmological implications

et al. 2019

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We find an argument related to the existence of a Z2-symmetry for the renormalization group flow derived from the bare Yang-Mills Lagrangian, and show that the cancellation of the vacuum energy may arise motivated both from the renormalization group flow solutions and the effective Yang-Mills action. In the framework of the effective Savvidy's action, two Mirror minima are allowed, with exactly equal and hold opposite sign energy densities. At the cosmological level, we explore the stability of the electric and magnetic attractor solutions, both within and beyond the perturbation theory, and find that thanks to these latter the cancellation between the electric and the magnetic vacua components is achieved at macroscopic space and time separations. This implies the disappearance of the conformal anomaly in the classical limit of an effective Yang-Mills theory. In this picture, the tunneling probability from the Mirror vacua to the other vacua is exponentially suppressed in the quantum non-thermal state -similarly to what happens for electroweak instantonic tunneling solutions. Specifically, we show that, in a dynamical Friedmann-Lemaître-Robertson-Walker (FLRW) cosmological background, the Nielsen-Olsen argument -on the instability of uniform chromo-electric and chromo-magnetic Mirror vacua -is subtly violated. The chromo-magnetic and chromo-electric uniform vacua are unstable only at asymptotic times, but at those times the attractor to a zero energy density is already reached. The two vacua can safely decay into one anisotropic vacuum that has zero energy-density inside the Fermi confinement volume scale. We also discover a new surprising pattern of solitonic and anti-solitonic space-like solutions, which are sourced by the Yang-Mills dynamics coupled to the Einstein's equations in FLRW. We dub such non-perturbative configurations, which are directly related to dynamical cancellation mechanism of the vacuum energy, as chronons, or χ-solutions.

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Section: Effective Ym Theory and The Mirror Symmetrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mirror symmetry of quantum Yang–Mills vacua and cosmological implications

et al. 2019

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“…[26]. From the group-theoretical viewpoint, the separation into spatially homogeneous and inhomogeneous components (A4) in the Minkowski spacetime has certain similarities with an analogical procedure in the conventional QCD instanton theory in Euclidean spacetime [31,32,37]. Namely, in both cases one performs a mapping of 3-space onto SU(2) subgroup elements of the color SU(3) c .…”

Section: Gauge Invariant Description Of a Coherent Su(2) Condensatementioning

confidence: 99%

Time-crystal ground state and production of gravitational waves from QCD phase transition *

2019

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We propose a novel mechanism for the production of gravitational waves in the early Universe that originates from the relaxation processes induced by the QCD phase transition. While the energy density of the quark-gluon mean-field is monotonously decaying in real time, its pressure undergoes a series of violent oscillations at the characteristic QCD time scales that generates a primordial multi-peaked gravitational waves signal in the radio frequencies' domain. The signal as an echo of the QCD phase transition, and is accessible by the FAST and SKA telescopes.

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“…One potentially important pathway involves the expression and activation of proton sensing G-protein Coupled Receptors (GPCR). Little is known about the role of the proton-sensing GPCRs in pulmonary fibrosis although they are increasingly recognized for being pathologically dysregulated in malignancy [20][21][22], heart failure [23], hypertension [24], pulmonary hypertension [25], irritable bowel disease [26][27][28], and asthma [25]. There are four members of this family of receptors, the Ovarian Cancer G-Protein Coupled Receptor Protein1 (OGR1, GPR68), G-protein Coupled Receptor 4 (GPR4), G2 accumulation (G2A), and T Cell Death-Associated Gene 8 (TDAG8) [29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

The Role of the Ovarian Cancer G -Coupled Receptor (OGR1) in Idiopathic Pulmonary Fibrosis

Nagel

Clough

Bell³

et al. 2019

Preprint

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Idiopathic pulmonary fibrosis (IPF) is a disease characterized by irreversible scarring of the lung that is associated with significant mortality and morbidity. The pathophysiology is incompletely understood but it is well-established that fibroblast to myofibroblast differentiation is a key feature of pulmonary fibrosis. Our lab has established that a reduction in extracellular pH is one of several important pathways responsible for the activation of latent TGF-β in the extracellular space. TGF-β activation further decreases extracellular pH and creates a feed-forward mechanism that stimulates myofibroblast differentiation and activation of additional TGF-β. Given the importance of TGF-β and extracellular acidification to the progression of pulmonary fibrosis, we sought to identify novel mechanisms that are involved in pH-dependent fibrotic signaling. The proton sensing G-Protein Coupled family of receptors are activated in acidic environments, but their role in fibrotic signaling has not been studied. Here we report that the Ovarian Cancer G-Protein Coupled Receptor1 (OGR1 or GPR68), a member of the family of proton sensing G-Protein Coupled Receptors, negatively regulates pro-fibrotic signaling.We demonstrate that OGR1 expression is significantly reduced in lung tissue from patients with IPF and TGF-β decreases OGR1 expression. In fibroblasts, a reduction in expression of OGR1 (OGR knockout lung fibroblasts) and knockdown (OGR siRNA), promotes in vitro myofibroblast differentiation. In contrast, OGR1 overexpression inhibits myofibroblast differentiation. Finally, we demonstrate that OGR1 negatively regulates TGF-β stimulation through inhibition of focal adhesion kinase (FAK) phosphorylation. Our results suggest that preserving OGR1 expression may represent a novel therapeutic strategy in pulmonary fibrosis.

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Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis

Abstract: OGR1 expression was correlated with increased expression levels of pro-fibrotic genes and collagen deposition. Ogr1 deficiency was associated with a decrease in fibrosis formation. Targeting OGR1 may be a potential new treatment option for IBD-associated fibrosis.

Cited by 35 publications

References 61 publications

Mirror symmetry of quantum Yang–Mills vacua and cosmological implications

Mirror symmetry of quantum Yang–Mills vacua and cosmological implications

Time-crystal ground state and production of gravitational waves from QCD phase transition *

The Role of the Ovarian Cancer G -Coupled Receptor (OGR1) in Idiopathic Pulmonary Fibrosis

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