Last update 01 Nov 2024

H-PGDS x CRTH2

Last update 01 Nov 2024

Basic Info

Related Targets

H-PGDSCRTH2

Drugs associated with H-PGDS x CRTH2

TM-30510

Target

CRTH2 x H-PGDS

Mechanism

CRTH2 antagonists [+1]

Active Org.-

Originator Org.

7TM Pharma

Active Indication-

Inactive Indication

Asthma [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ADC-7405

Target

CRTH2 x H-PGDS

Mechanism

CRTH2 antagonists [+1]

Active Org.-

Originator Org.

Pulmagen Therapeutics LLP

Active Indication-

Inactive Indication

Asthma

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with H-PGDS x CRTH2

100 Translational Medicine associated with H-PGDS x CRTH2

0 Patents (Medical) associated with H-PGDS x CRTH2

376

Literatures (Medical) associated with H-PGDS x CRTH2

01 Nov 2024·Ecotoxicology and Environmental Safety

Unraveling cadmium-driven liver inflammation with a focus on arachidonic acid metabolites and TLR4/ IκBα /NF-κB pathway

Article

Author: Gong, Xun ; Liu, Junlin ; Guo, Chuanzhi ; Shi, Haifeng ; Tang, Min ; Gu, Jie ; Ruan, Jiacheng ; Li, Zehua

Epidemiological studies have demonstrated exposure to cadmium ion (Cd²⁺) is significantly associated with the incidence and aggravation of nonalcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). Cd²⁺ exposure could alter lipid metabolism, and changed lipid metabolites are significantly associated with NASH. Arachidonic acid (ArA) is an omega-6 polyunsaturated fatty acid. Promotion of ArA synthesis and profile changes by Cd²⁺ exposure potentially to cause NAFLD. ArA metabolism pathway has been identified to enrich in Cd²⁺ exposure-facilitated NASH. ArA could be generation an impressive metabolic profile through mainly three pathways, including Cyclooxygenases (COX), Lipoxygenases (LOX) and Cytochrome P450 (CYP450) pathway. However, the functions of these metabolites and underlying mechanism in hepatic inflammation are still not clear. In present study, by integrative transcriptomics and metabolomics analysis, we identified that the fatty acid metabolic process and the pro-inflammatory NF-κB signaling pathway were enriched in Cd²⁺-regulated differentially expressed genes (DEGs) and Cd²⁺-altered differential metabolites, such as, fatty acid biosynthesis, degradation, and ArA metabolism. The metabolites levels of LOX pathway products 5-HETE and leukotriene C4 (LTC4), and COX catalytic product prostaglandin D2 (PGD2) were significantly elevated in Cd²⁺ exposed mouse livers. 5-HETE, LTC4, and PGD2 were significantly positive correlated with NF-κB signaling. In addition, the synthase of 20-Hydroxyeicosatetraenoic acid (20-HETE), CYP450 gene 4 family (CYP4A32), was also involved in NF-κB signaling network. Results from both in vitro and in vivo proved that Cd²⁺ exposure increased ArA metabolite to PGD2 and 20-HETE, and upregulated the mRNA level of their catalytic enzyme PGDS and CYP4A32. Cd²⁺-induced ArA metabolite to PGD2 and 20-HETE promoted activation of TLR4/IκBα/NF-κB signaling and pro-inflammatory of hepatocytes. Our study explores novel molecular mechanism of Cd²⁺ exposure-aggravated liver diseases and provides potential novel targets for in hepatic inflammatory treatments and prevention.

01 Aug 2024·Journal of Affective Disorders

Astrocyte atrophy induced by L-PGDS/PGD2/Src signaling dysfunction in the central amygdala mediates postpartum depression

Article

Author: Song, Yujie ; Sheng, Zhihao ; Liu, Qidong ; Ye, Binglu ; Liu, Jinqi ; Liu, Zhiqiang ; Zhang, Bing ; Du, Weijia ; Guo, Fei ; Li, Siguang ; Xu, Zhendong ; Song, Yingcai ; Li, Yujie

BACKGROUNDPostpartum depression (PPD) is a serious psychiatric disorder that has significantly adverse impacts on maternal health. Metabolic abnormalities in the brain are associated with numerous neurological disorders, yet the specific metabolic signaling pathways and brain regions involved in PPD remain unelucidated.METHODSWe performed behavioral test in the virgin and postpartum mice. We used mass spectrometry imaging (MSI) and targeted metabolomics analyses to investigate the metabolic alternation in the brain of GABA_AR Delta-subunit-deficient (Gabrd^-/-) postpartum mice, a specific preclinical animal model of PPD. Next, we performed mechanism studies including qPCR, Western blot, immunofluorescence staining, electron microscopy and primary astrocyte culture. In the specific knockdown and rescue experiments, we injected the adeno-associated virus into the central amygdala (CeA) of female mice.RESULTSWe identified that prostaglandin D2 (PGD2) downregulation in the CeA was the most outstanding alternation in PPD, and then validated that lipocalin-type prostaglandin D synthase (L-PGDS)/PGD2 downregulation plays a causal role in depressive behaviors derived from PPD in both wild-type and Gabrd^-/- mice. Furthermore, we verified that L-PGDS/PGD2 signaling dysfunction-induced astrocytes atrophy is mediated by Src phosphorylation both in vitro and in vivo.LIMITATIONSL-PGDS/PGD2 signaling dysfunction may be only responsible for the depressive behavior rather than maternal behaviors in the PPD, and it remains to be seen whether this mechanism is applicable to all depression types.CONCLUSIONOur study identified abnormalities in the L-PGDS/PGD2 signaling in the CeA, which inhibited Src phosphorylation and induced astrocyte atrophy, ultimately resulting in the development of PPD in mice.

08 Apr 2024·JCI Insight

Single-cell molecular signature of pathogenic T helper subsets in type 2–associated disorders in humans

Article

Author: Nutman, Thomas B ; Dulek, Brittany ; Lack, Justin ; Swanson, Phillip ; Gazzinelli-Guimaraes, Pedro H ; Roederer, Mario

To unravel the heterogeneity and molecular signature of effector memory Th2 cells (Tem2), we analyzed 23 individuals' PBMCs of filaria-infected (Filaria+) and 24 healthy volunteers (Filaria-), with or without coincident house dust mite (HDM) allergic sensitization. Flow cytometry revealed 3 CD4+ Tem subsets - CCR4+CCR6+CRTH2- Tem17, CCR4+CCR6-CRTH2+ Tem2, and CCR6+CCR4+CRTH2+ Tem17.2 - markedly enriched in Filaria+ individuals. These subsets were sorted and analyzed by multiomic single-cell RNA immunoprofiling. SingleR-annotated Th2 cells from Tem2 and Tem17.2 cell subsets had features of pathogenic Th2 effector cells based on their transcriptional signatures, with downregulated CD27 and elevated expression levels of ITGA4, IL17RB, HPGDS, KLRB1, PTGDR2, IL9R, IL4, IL5, and IL13 genes. When the Filaria+ individuals were subdivided based on their allergic status, Tem2 cells in HDM+Filaria+ individuals showed an overall reduction in TCR diversity, suggesting the occurrence of antigen-driven clonal expansion. Moreover, HDM+Filaria+ individuals showed not only an expansion in the frequency of both Tem2 and Tem17.2 cell subsets, but also a change in their molecular program by overexpressing GATA3, IL17RB, CLRF2, and KLRB1, as well as increased antigen-induced IL-4, IL-5, and IL-13 production, suggesting that aeroallergens reshape the transcriptional and functional programming of Th2 cell subsets in human filarial infection toward a pathogenic immunophenotype.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis