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Chemical Systems Biology Reveals Mechanisms of Dissociated Glucocorticoid Receptor Signaling

ABSTRACT: Chemical Systems Biology Reveals Mechanisms of Dissociated Glucocorticoid Receptor Signaling

PROVIDER: PRJNA628707 | ENA |

REPOSITORIES: ENA

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Chemical Systems Biology Reveals Mechanisms of Dissociated Glucocorticoid Receptor Signaling

Project description:Glucocorticoids display remarkable anti-inflammatory activity, but their use is limited by undesirable on-target effects including insulin resistance and skeletal muscle atrophy. We used a chemical systems biology approach called Ligand Class Analysis (LCA) to examine ligands designed to alter the receptor through distinct structural mechanisms. These ligands displayed a full range of activity profiles, providing the variance required to identify ligand-specific gene expression and transcriptional coregulator interaction patterns that were highly predictive of their effects on myocyte glucose disposal and protein balance. Anti-inflammatory effects were linked to inhibition of glucose disposal in skeletal muscle but not to muscle atrophy. This approach successfully predicted dissociated activity in vivo, identifying compounds that were muscle sparing or anabolic for protein balance and mitochondrial potential. LCA defines the mechanistic links between the ligand-receptor interface and the physiological outcomes of the ligands, a general approach that can be applied to any ligand-regulated allosteric signaling system.

2020-09-08 | GSE149453 | GEO

Chemical systems biology reveals mechanisms of glucocorticoid receptor signaling.

Project description: Not available

| S-EPMC8783757 | biostudies-literature

Effect of glucocorticoid chemical structure and receptor potency on human trabecular meshwork cells

Project description:Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells. Gene expression changes of human trabecular meshwork cells, TM 86 and TM 93, due to treatment with dexamethasone (Dex), fluocinolone acetonide (FA), and triamcinolone acetonide (TA).

2010-02-15 | GSE16643 | GEO

Systems biology of prostate cancer

Project description:Systems biology of prostate cancer

| PRJEB34826 | ENA

A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis

Project description:A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis

| PRJNA471889 | ENA

A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis [microarray]

Project description:BACKGROUND: Glucocorticoid (GC) refractoriness is a common and unpredictable phenomenon in ulcerative colitis (UC). Although it has been demonstrated that NFkB is involved in its mechanism of action (MoA), there are no conclusive studies on the molecular functions involved. The current study describes in depth the MoA related to GC failure, by integrating transcriptomic data from UC patients, and updated molecular data on UC and GC. METHODS: miRNA and mRNA expression from rectal biopsies of active UC patients, obtained before and on the 3rd day of GC treatment, were evaluated by sequencing and microarrays, respectively. The differential results obtained were integrated into the mathematical models generated by Systems Biology. RESULTS: This computational approach identified 64 proteins, among which 18 stand out, either by being associated to the MoA or by providing a major capacity to classify the patients according to GC response. The biological functions of these proteins have been linked with inflammation, machinery GC-induced transcription and angiogenesis. All the selected proteins but one —Acidic leucine-rich Nuclear Phosphoprotein 32 family member E (ANP32E) — had previously been related to UC and/or GC-induced biological actions. ANP32E has been linked to the exchange of H2A to H2A.z histone, which promotes CG receptor complex-activated transcription. Western blot and immunofluorescence assays confirmed the predictive results obtained by Systems Biology. CONCLUSIONS: A comprehensive MoA of GC refractoriness has been described, highlighting the key role of GC-induced transcription in this phenomenon. Several proteins have been identified as putative predictors of GC refractoriness.

2018-11-06 | GSE114527 | GEO

A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis [miRNA-Seq]

2018-11-06 | GSE114591 | GEO

A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis [microarray]

Project description:A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis [microarray]

| PRJNA471688 | ENA

Computational systems chemical biology.

Project description: Not available

| S-EPMC3547368 | biostudies-literature

A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis [miRNA-Seq]

Project description:A systems biology approach identifies ANP32E and other biomarkers of glucocorticoid refractoriness in ulcerative colitis [miRNA-Seq]

| PRJNA471862 | ENA

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