GEO DataSets

(Submitter supplied) Cardiac fibrosis is the final common pathology in heart disease. Here we establish an integrated imaging-genomic discovery platform using primary human heart fibroblasts to identify new drug targets for cardiac fibrosis. Genome wide analyses identify IL11, a secreted cytokine amenable to therapeutic inhibition, as the leading pro-fibrotic candidate. We demonstrate an autocrine loop of IL11 activity that is critical for fibrosis and acts as a nexus of signalling convergence for multiple pro-fibrotic stimuli. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

18 Samples

Download data: TXT

(Submitter supplied) Fibrosis is a common pathology in cardiovascular disease. In the heart, fibrosis causes mechanical and electrical dysfunction and in the kidney, it predicts the onset of renal failure. Transforming growth factor β1 (TGFβ1) is the principal pro-fibrotic factor, but its inhibition is associated with side effects due to its pleiotropic roles. We hypothesized that downstream effectors of TGFβ1 in fibroblasts could be attractive therapeutic targets and lack upstream toxicity. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

2 Samples

Download data: CSV

(Submitter supplied) Cardiac fibrosis is the final common pathology in heart disease. Here we establish an integrated imaging-genomic discovery platform using primary human heart fibroblasts to identify new drug targets for cardiac fibrosis. Genome wide analyses identify IL11, a secreted cytokine amenable to therapeutic inhibition, as the leading pro-fibrotic candidate. We demonstrate an autocrine loop of IL11 activity that is critical for fibrosis and acts as a nexus of signalling convergence for multiple pro-fibrotic stimuli. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

168 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL16791 GPL19057 GPL18573

212 Samples

Download data: CSV

(Submitter supplied) Cardiac fibrosis is the final common pathology in heart disease. Here we establish an integrated imaging-genomic discovery platform using primary human heart fibroblasts to identify new drug targets for cardiac fibrosis. Genome wide analyses identify IL11, a secreted cytokine amenable to therapeutic inhibition, as the leading pro-fibrotic candidate. We demonstrate an autocrine loop of IL11 activity that is critical for fibrosis and acts as a nexus of signalling convergence for multiple pro-fibrotic stimuli. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

24 Samples

Download data: TXT

(Submitter supplied) Background and aims: Here we investigate the role of IL-11 signalling in the pathogenesis of nonalcoholic steatohepatitis (NASH). Methods: HSCs or hepatocytes were stimulated with IL-11 and effects assessed using cellular and high content imaging, immunoblotting, ELISA and invasion assays. Genetic and pharmacological IL-11 gain- or loss-of-function experiments were performed in vitro and in vivo. IL-11 signaling was studied using ERK inhibitors. more...

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL18573 GPL19057

30 Samples

Download data: TXT

(Submitter supplied) Objectives: Interleukin 11 (IL11) is highly upregulated in skin and lung fibroblasts from patients with systemic sclerosis (SSc). Here we tested whether IL11 is mechanistically linked with human dermal fibroblast (HDF) activation. Methods: We measured serum IL11 levels in healthy volunteers and patients with early diffuse SSc and manipulated IL11 signalling in HDFs using gain- and loss-of-function approaches. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

4 Samples

Download data: TXT

(Submitter supplied) To recognize the influnence of WNT signaling on fibroblasts differentiation first we analyzed transformation of human cardiac fibroblasts caused by TGF-β signaling. Differential gene expression analysis demonstrated that cardiac fibroblasts 72h after treatment with TGF-β showed deregulated expression of 313 genes. We also observed that stimulation with WNT3a resulted in deregulation of 124 genes in TGF-β-treated fibroblasts and in contrast to profound effect of WNT3a on fibroblasts differentiation, treatment with WNT5a upregulated expression of only 2 and downregulated 21 genes in TGF-β-activated cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

12 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL11154

70 Samples

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(Submitter supplied) Background: Fibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global post-transcriptional mechanisms underlying fibroblast-to-myofibroblast conversion in the heart have not been explored. Methods: Genome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL11154

30 Samples

Download data: TXT

(Submitter supplied) Cardiac fibroblasts from 4 patients treated for up to 24 hours with TGFB1

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL11154

40 Samples

Download data: TXT

(Submitter supplied) Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease where invasive pulmonary myofibroblasts secrete collagen and destroy lung integrity. Here we show that IL-11 is upregulated in the lung of IPF patients, associated with disease severity and is secreted from IPF fibroblasts. In vitro, IL-11 stimulates lung fibroblasts to become invasive, ACTA2+ve, collagen secreting myofibroblasts, in an ERK-dependent fashion. more...

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL19057 GPL18573

39 Samples

Download data: TXT

(Submitter supplied) Interleukin (IL)-11 is a member of the IL-6 family of cytokines and involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generated Il11 reporter mice. IL-11+ cells appeared in the colon of murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuated the development of colitis-associated colorectal cancer. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL25723

6 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by array; Expression profiling by high throughput sequencing

Platforms:

GPL25723 GPL21163

11 Samples

Download data: TXT

(Submitter supplied) Interleukin (IL)-11 belongs to a member of the IL-6 family of cytokines and is involved in a variety of cellular responses. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generated Il11 reporter mice. IL-11+ cells rapidly appeared in the colon of mice after dextran sulfate sodium treatment. IL-11+ cells expressed fibroblast markers and genes associated with cell proliferation and tissue repair. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL21163

5 Samples

Download data: TXT

(Submitter supplied) Background: Organ fibrosis due to excessive production of extracellular matrix (ECM) by resident fibroblasts is estimated to contribute to >45% of deaths in the Western world, including those due to cardiovascular diseases such as heart failure (HF). Here, we screened for small molecule inhibitors with a common ability to suppress activation of fibroblasts across organ systems. Methods: High content imaging of cultured cardiac, pulmonary and renal fibroblasts was employed to identify non-toxic compounds that blocked induction of markers of activation in response to the profibrotic stimulus, TGF-β. more...

Organism:

Rattus norvegicus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL25947

16 Samples

Download data: XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

8 Samples

Download data: TXT

(Submitter supplied) Orbital fibrosis is a hallmark of tissue remodeling in thyroid-associated ophthalmopathy (TAO). Previous studies have shown that interleukin (IL)-11 plays a pivotal profibrotic role in various inflammatory and autoimmune diseases. However, the expression pattern of IL-11 in patients with TAO and whether IL-11 is mechanistically linked with pathological fibrosis remains unknown. In this study, we investigated IL-11 levels in the serum and orbital connective tissue of patients with TAO, and evaluated the correlation of these levels with the patient’s clinical activity score. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

2 Samples

Download data: TXT

(Submitter supplied) Orbital fibrosis is a hallmark of tissue remodeling in thyroid-associated ophthalmopathy (TAO). Previous studies have shown that interleukin (IL)-11 plays a pivotal profibrotic role in various inflammatory and autoimmune diseases. However, the expression pattern of IL-11 in patients with TAO and whether IL-11 is mechanistically linked with pathological fibrosis remains unknown. In this study, we investigated IL-11 levels in the serum and orbital connective tissue of patients with TAO, and evaluated the correlation of these levels with the patient’s clinical activity score. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

6 Samples

Download data: TXT

(Submitter supplied) The kidney has large regenerative capacity that is impeded when injured renal tubular epithelial cells (TECs) undergo SNAI1-driven partial epithelial mesenchymal transition (pEMT). Here we investigate the role of IL11 in TEC pEMT and kidney repair. Wild-type mice with acute kidney injury (AKI) upregulate IL11 in TECs triggering an ERK/P90RSK/GSK3β axis of SNAI1 expression leading to impaired renal function, which is abrogated in Il11 null mice. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

16 Samples

Download data: TXT