Limits...
Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response.

Cohen PY, Breuer R, Zisman P, Wallach-Dayan SB - Mediators Inflamm. (2015)

Bottom Line: Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM) components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions.Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu.Inflammation is not essential for evolution of fibrosis as was previously stated.

View Article: PubMed Central - PubMed

Affiliation: Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.

ABSTRACT
Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1(-)) myofibroblasts was shown in the lungs of humans with idiopathic pulmonary fibrosis (IPF) and of bleomycin-treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1-deficiency, in vivo, in bleomycin-injured mouse lungs. Thy1 increased in mouse lung lymphocytes following bleomycin injury but decreased in myofibroblasts when fibrosis was at the highest point (14 days), as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM) components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions. Chimeric Thy1-deficient mice with Thy1(+) lymphocytes and Thy1(-) myofibroblasts showed fibrosis similar to wild-type mice and an increased number of CD4/CD25 regulatory T cells, with a concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu. Inflammation is not essential for evolution of fibrosis as was previously stated.

No MeSH data available.


Related in: MedlinePlus

The number of genes in lung myofibroblasts with significant changes in expression at varying time points following Thy1 stimulation. Graphic presentation of GeneChip microarray results obtained from primary myofibroblast RNA extracts following stimulation with G7 anti-Thy mAb (5 μg/mL) or control IgG isotype for 30 min, 1 h, 6 h, or 24 h. The microarray data were processed by volcano analysis. Upregulated genes (blue), downregulated genes (red).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4537759&req=5

fig2: The number of genes in lung myofibroblasts with significant changes in expression at varying time points following Thy1 stimulation. Graphic presentation of GeneChip microarray results obtained from primary myofibroblast RNA extracts following stimulation with G7 anti-Thy mAb (5 μg/mL) or control IgG isotype for 30 min, 1 h, 6 h, or 24 h. The microarray data were processed by volcano analysis. Upregulated genes (blue), downregulated genes (red).

Mentions: To assess the effects of Thy1 activation on lung myofibroblasts, we analyzed gene expression patterns using GeneChip microarrays (Affymetrix, Santa Clara, CA, USA) in samples of RNA extracted from lung primary lung myofibroblasts at different time points before and after Thy1 crosslinking by G7 anti-Thy1 mAb 10 μg/mL G7, compared to crosslinking with control matched-IgG isotype, for 30 min and 1, 6, and 24 hours. Genes with significant expression changes following Thy1 crosslinking-induced activation were detected following volcano analysis, using a threshold of >2-fold changes of gene expression over the untreated control and P < 0.05 as the test for significance. Most changes occurred very quickly, from 30 min-to-1 h following Thy1 stimulation. The number of downregulated genes was larger than the number that was upregulated (Figure 2).


Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response.

Cohen PY, Breuer R, Zisman P, Wallach-Dayan SB - Mediators Inflamm. (2015)

The number of genes in lung myofibroblasts with significant changes in expression at varying time points following Thy1 stimulation. Graphic presentation of GeneChip microarray results obtained from primary myofibroblast RNA extracts following stimulation with G7 anti-Thy mAb (5 μg/mL) or control IgG isotype for 30 min, 1 h, 6 h, or 24 h. The microarray data were processed by volcano analysis. Upregulated genes (blue), downregulated genes (red).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537759&req=5

fig2: The number of genes in lung myofibroblasts with significant changes in expression at varying time points following Thy1 stimulation. Graphic presentation of GeneChip microarray results obtained from primary myofibroblast RNA extracts following stimulation with G7 anti-Thy mAb (5 μg/mL) or control IgG isotype for 30 min, 1 h, 6 h, or 24 h. The microarray data were processed by volcano analysis. Upregulated genes (blue), downregulated genes (red).
Mentions: To assess the effects of Thy1 activation on lung myofibroblasts, we analyzed gene expression patterns using GeneChip microarrays (Affymetrix, Santa Clara, CA, USA) in samples of RNA extracted from lung primary lung myofibroblasts at different time points before and after Thy1 crosslinking by G7 anti-Thy1 mAb 10 μg/mL G7, compared to crosslinking with control matched-IgG isotype, for 30 min and 1, 6, and 24 hours. Genes with significant expression changes following Thy1 crosslinking-induced activation were detected following volcano analysis, using a threshold of >2-fold changes of gene expression over the untreated control and P < 0.05 as the test for significance. Most changes occurred very quickly, from 30 min-to-1 h following Thy1 stimulation. The number of downregulated genes was larger than the number that was upregulated (Figure 2).

Bottom Line: Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM) components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions.Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu.Inflammation is not essential for evolution of fibrosis as was previously stated.

View Article: PubMed Central - PubMed

Affiliation: Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.

ABSTRACT
Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1(-)) myofibroblasts was shown in the lungs of humans with idiopathic pulmonary fibrosis (IPF) and of bleomycin-treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1-deficiency, in vivo, in bleomycin-injured mouse lungs. Thy1 increased in mouse lung lymphocytes following bleomycin injury but decreased in myofibroblasts when fibrosis was at the highest point (14 days), as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM) components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions. Chimeric Thy1-deficient mice with Thy1(+) lymphocytes and Thy1(-) myofibroblasts showed fibrosis similar to wild-type mice and an increased number of CD4/CD25 regulatory T cells, with a concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu. Inflammation is not essential for evolution of fibrosis as was previously stated.

No MeSH data available.


Related in: MedlinePlus