The Role of STAT 3 in Tissue Fibrosis

Li, Ma; Zhuang, Songlin

doi:10.2174/187231311793564342

Cited by 4 publications

(4 citation statements)

References 68 publications

(86 reference statements)

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“…It is conceivable, that disc/bone marrow coupling induces fibrogenic changes of the bone marrow as well. This is supported by the disc/marrow correlation of several genes associated with tissue fibrosis (COL1A, IL4, and STAT3) 24,27 . Chronic TLR-signaling generally accompanies chronic injuries and fibrosis 28 .…”

Section: Discussionmentioning

confidence: 82%

ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes

et al. 2017

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Study design Cross-sectional cohort analysis of patients with Modic Changes (MC). Objective Our goal was to characterize the molecular and cellular features of MC bone marrow and adjacent discs. We hypothesized that MC associate with biologic cross-talk between discs and bone marrow, the presence of which may have both diagnostic and therapeutic implications. Background Data MC are vertebral bone marrow lesions that can be a diagnostic indicator for discogenic low back pain. Yet, the pathobiology of MC is largely unknown. Methods Patients with Modic type 1 or 2 changes (MC1, MC2) undergoing at least 2-level lumbar interbody fusion with one surgical level having MC and one without MC (control level). Two discs (MC, control) and two bone marrow aspirates (MC, control) were collected per patient. Marrow cellularity was analyzed using flow cytometry. Myelopoietic differentiation potential of bone marrow cells was quantified to gauge marrow function, as was the relative gene expression profiles of the marrow and disc cells. Disc/bone marrow cross-talk was assessed by comparing MC disc/bone marrow features relative to unaffected levels. Results Thirteen MC1 and eleven MC2 patients were included. We observed pro-osteoclastic changes in MC2 discs, an inflammatory dysmyelopoiesis with fibrogenic changes in MC1 and MC2 marrow, and upregulation of neurotrophic receptors in MC1 and MC2 bone marrow and discs. Conclusion Our data reveal a fibrogenic and pro-inflammatory cross-talk between MC bone marrow and adjacent discs. This provides insight into the pain generator at MC levels and informs novel therapeutic targets for treatment of MC-associated LBP.

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Section: Discussionmentioning

confidence: 82%

ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes

et al. 2017

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“…To assess GBS specific actions of GR cofactors, we knocked down expression of SWI/SNF subunit Brahma (Brm) (12) and coactivator-associated arginine methyltransferase 1 (CARM1) (13). Knock-down of CARM1 reduced activation for each GBS tested (Fig.…”

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confidence: 99%

DNA Binding Site Sequence Directs Glucocorticoid Receptor Structure and Activity

Meijsing

Pufall

et al. 2009

Science

632

723

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Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes are modulated so precisely is not well understood. The glucocorticoid receptor (GR) regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes. Traditionally, these binding sites have been viewed only as docking sites. Using structural, biochemical, and cell-based assays, we show that GR binding sequences, differing by as little as a single base pair, differentially affect GR conformation and regulatory activity. We therefore propose that DNA is a sequence-specific allosteric ligand of GR that tailors the activity of the receptor toward specific target genes.

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“…For example, TFICA associates HNF4G with metabolic disorders, which corresponds to its KEGG annotation. STAT3's role in fibrotic diseases is well-studied, as it is implicated in the proliferation of fibroblasts and excess ECM proteins [30] . In total, the network visualization describes 491 relationships, 33 are known associations according GAD, OMIM, and GWAS Catalog and thus the remaining 458 are potentially novel transcription factor-disease relationships.…”

Section: Resultsmentioning

confidence: 99%

Coherent Functional Modules Improve Transcription Factor Target Identification, Cooperativity Prediction, and Disease Association

et al. 2014

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Transcription factors (TFs) are fundamental controllers of cellular regulation that function in a complex and combinatorial manner. Accurate identification of a transcription factor's targets is essential to understanding the role that factors play in disease biology. However, due to a high false positive rate, identifying coherent functional target sets is difficult. We have created an improved mapping of targets by integrating ChIP-Seq data with 423 functional modules derived from 9,395 human expression experiments. We identified 5,002 TF-module relationships, significantly improved TF target prediction, and found 30 high-confidence TF-TF associations, of which 14 are known. Importantly, we also connected TFs to diseases through these functional modules and identified 3,859 significant TF-disease relationships. As an example, we found a link between MEF2A and Crohn's disease, which we validated in an independent expression dataset. These results show the power of combining expression data and ChIP-Seq data to remove noise and better extract the associations between TFs, functional modules, and disease.

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The Role of STAT 3 in Tissue Fibrosis

Cited by 4 publications

References 68 publications

ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes

ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes

DNA Binding Site Sequence Directs Glucocorticoid Receptor Structure and Activity

Coherent Functional Modules Improve Transcription Factor Target Identification, Cooperativity Prediction, and Disease Association

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