Project description:To investigate class A G protein-coupled receptors (GPCR)-targeted drugs in the regulation of osteogenic differentiation, we investigated the effects of drugs using mesenchymal stromal cells. By applying microarray dataset, we idntified the mRNA expressions profiles in hDPSCs.

2023-01-20 | GSE217436 | GEO

Targeting class A GPCRs for hard tissue regeneration [ATAC-seq]

2023-01-20 | GSE217264 | GEO

Targeting class A GPCRs for hard tissue regeneration [RNA-seq]

Project description:To investigate class A G protein-coupled receptors (GPCR)-targeted drugs in the regulation of osteogenic differentiation, we investigated the effects of drugs using mesenchymal stromal cells. We conducted whole-transcriptome analysis using bulk RNA sequencing (RNA-seq) of six drugs.

2023-01-20 | GSE217371 | GEO

Targeting class A GPCRs for hard tissue regeneration

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-01-20 | GSE217437 | GEO

First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure

Project description:<p>Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance [NMR] spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i). MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85% hepatectomy model, and showed antisteatotic and antifibrotic effects in liver disease mouse models. A first-in-human phase I trial (European Union Drug Regulating Authorities Clinical Trials [EudraCT] 2021-000193-28) with the clinical candidate HRX215 was conducted and revealed excellent safety and pharmacokinetics. Clinical trials to probe HRX215 for prevention/treatment of liver failure after extensive oncological liver resections or after transplantation of small grafts are warranted.</p>

2024-09-23 | MTBLS9434 | MetaboLights

Microarray hybridization data from the root tips of 5-day-old Arabidopsis thaliana seedlings grown on tilted, hard agar surfaces

Project description:The growth behavior of plant roots on tilted, hard agar surfaces is determined by many basic cellular processes, including microtubule dynamics and cell wall expansion. Among Arabidopsis thaliana accessions there is natural variation for these behaviors, including one known as skewing or slanting. The root skewing pattern on hard, tilted agar surfaces may be a clue to adaptations of an accession to its environment. Here, we compare expression profiles of two accessions with diverse skewing behavior grown on the wave assay, which consists of seedlings growing two days vertically and 3 days tilted on hard agar plates. Cvi has a strong skew on tilted, hard agar sufaces, and Ler-2 has a weaker one. We also include a near isogenic line, 170G-55-16 a.k.a HGI2.1, that is mostly Ler-2 in background but has a segment of Cvi introgressed into chromosome 2. This line has an intermediate skew between its two parents.

2011-03-31 | GSE28275 | GEO

Endocytosis sculpts distinct cAMP signal transduction by endogenously coexpressed GPCRs

Project description:Many G protein-coupled receptors (GPCRs) trigger a second phase of G protein-dependent signaling from internal membranes after agonist-induced endocytosis. However, individual GPCRs differ significantly in their ability to internalize after activation, and it remains unclear if this confers selectivity on cellular signaling through natively coexpressed GPCRs. We addressed this question by examining the activation of the cyclic AMP (cAMP) / cAMP-dependent protein kinase (PKA) pathway by three ligands that stimulate three distinct, endogenously coexpressed GPCRs in HEK293 cells: isoproterenol (Iso) which primarily activates the β2-adrenergic receptor (β2AR), vasoactive intestinal peptide (VIP) which primarily activates the vasoactive intestinal peptide receptor 1 (VIPR1/VPAC1), and 5'-N-ethylcarboxamidoadenosine (NECA) which primarily activates the adenosine 2B receptor (A2BR). Using location-targeted biosensors and a transcriptional reporter, we demonstrate that each ligand triggers a unique cellular signaling profile and that these responses are differentially sensitive to endocytic inhibition. VIP elicited a response that was endocytosis-dependent at every level in the pathway tested, from upstream global cAMP elevation to downstream activation of nuclear PKA, while Iso elicited a response that was dependent on endocytosis selectively at downstream steps. In contrast, NECA robustly activated the entire cAMP signaling cascade independently of endocytosis, consistent with our observation that human A2BR does not robustly internalize after activation. We conclude that endocytosis indeed sculpts downstream cAMP signaling by GPCRs in a receptor-specific manner. Our results add to the evolving view of compartmentalized signaling in the cAMP / PKA pathway and suggest that differences in GPCR trafficking can encode receptor-specific signaling profiles through a shared signal transduction pathway.

2025-02-24 | GSE290019 | GEO

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