Identification of glucocorticoid‐regulated genes that control cell proliferation during murine respiratory development

Bird, Anthony Daniel; Tan, Kian L.; Olsson, Fredrik Par; Zieba, Malgorzata; Flecknoe, Sharon Jayne; Liddicoat, Douglas; Mollard, Richard Anthony; Hooper, Stuart B.; Cole, Timothy J.

doi:10.1113/jphysiol.2007.136796

Cited by 46 publications

(42 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In normal lung array data, the serine protease CELA1 increased threefold between E12 and PND1, and gene expression remained at that level through adulthood (22). In glucocorticoid receptor-null mouse lung array data, at E18.5, expression of CELA1 was reduced 9.4-fold compared with wild type, and PCR confirmation demonstrated a 25-fold decrease in CELA1 mRNA (7). Microarray data demonstrated no differences in CELA1 expression in the hyperoxia model of impaired lung development (12).…”

Section: Temporal-spatial Changes In Elastin Remodeling During Sacculmentioning

confidence: 96%

“…In a mouse pup mechanical ventilation model, inhibition of neutrophil elastase improves alveolar septation (18). While investigating the effect of glucocorticoid-receptor signaling on lung cell proliferation during embryonic lung development, Bird et al found a 25-fold reduction in mRNA levels of the pancreatic serine protease chymotrypsin-like elastase 1 (CELA1) (7). Published microarray data of normally developing mouse lung demonstrated increased CELA1 mRNA starting at embryonic day 14 (22).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Dynamic expression of chymotrypsin-like elastase 1 over the course of murine lung development

Liu

Young

Varisco

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

-Postnatal lung development requires coordination of three processes (surface area expansion, microvascular growth, and matrix remodeling). Because normal elastin structure is important for lung morphogenesis, because physiological remodeling of lung elastin has never been defined, and because elastin remodeling is angiogenic, we sought to test the hypothesis that, during lung development, elastin is remodeled in a defined temporal-spatial pattern, that a novel protease is associated with this remodeling, and that angiogenesis is associated with elastin remodeling. By elastin in situ zymography, lung elastin remodeling increased 24-fold between embryonic day (E) 15.5 and postnatal day (PND) 14. Remodeling was restricted to major vessels and airways on PND1 with a sevenfold increase in alveolar wall elastin remodeling from PND1 to PND14. By inhibition assays and literature review, we identified chymotrypsin-like elastase 1 (CELA1) as a potential mediator of elastin remodeling. CELA1 mRNA levels increased 12-fold from E15.5 to PND9, and protein levels increased 3.4-fold from E18.5 to PND9. By costaining experiments, the temporal-spatial pattern of CELA1 expression matched that of elastin remodeling, and 58 -85% of CELA1 ϩ cells were Ͻ10 m from an elastase signal. An association between elastin remodeling and angiogenesis was tested by similar methods. At PND7 and PND14, 60 -95% of angiogenin ϩ cells were associated with elastin remodeling. Both elastase inhibition and CELA1 silencing impaired angiogenesis in vitro. Our data defines the temporal-spatial pattern of elastin remodeling during lung development, demonstrates an association of this remodeling with CELA1, and supports a role for elastin remodeling in regulating angiogenesis. matrix remodeling; elastin; pulmonary vascular development THREE COORDINATED PROCESSES occur during the saccular and alveolar stages of lung development that are critical to meeting the metabolic demands of ex utero life. Airway branching and septation dramatically increase gas exchange surface area, expansion of the pulmonary microvasculature increases perfusion capacity to match this increased surface area, and matrix remodeling and epithelial thinning increase gas diffusion capacity. Multiple studies have demonstrated that these three processes are intertwined. Microvascular development is necessary for alveolar septation (21), and models of impaired alveolar septation have marked pruning of the pulmonary vasculature (24). Reduced matrix metalloproteinase (MMP)-2 and MMP14 activity impairs alveolar septation (4, 30), and pulmonary epithelial cells (30), vascular cells (37), and macrophages (26) all remodel lung matrix during saccular and alveolar lung development. Because elastin plays a critical mechano-developmental role in the lung (1), and remodeling of elastin is angiogenic (31-33), we asked whether elastin remodeling might provide a mechanistic link between matrix remodeling, alveolar growth, and microvascular expansion.

show abstract

Section: Temporal-spatial Changes In Elastin Remodeling During Sacculmentioning

confidence: 96%

mentioning

confidence: 99%

Dynamic expression of chymotrypsin-like elastase 1 over the course of murine lung development

Liu

Young

Varisco

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…39) In addition, it has been reported that GR regulates various gene transcription. 40) Transcription activity of some genes related to cell cycle, such as cyclin, might be altered by CORT treatment. 41) In contrast, the expression level of MR did not change in either the cytosol or nuclear fraction.…”

Section: Discussionmentioning

confidence: 99%

Corticosterone Suppresses the Proliferation of RAW264.7 Macrophage Cells via Glucocorticoid, But Not Mineralocorticoid, Receptor

Nakatani

Amano

Takeda

2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Macrophages are white blood cells within tissues that are produced by monocytes and help to protect against infection by bacteria through phagocytosis. Several studies have shown a correlation between the state of depression and abnormalities in the immune response. Corticosterone (CORT), which is often referred to as the stress hormone, is a well-known regulator of peripheral immune responses and also shows anti-inflammatory properties in the body. However, it is still unclear how CORT regulates macrophage function. In this study, we focused on the effects of CORT on the proliferation and survival of macrophage cells using the macrophage cell line RAW264.7. Under treatment with 10 µm CORT for 24 h, the proliferation of RAW264.7 cells decreased to 73.6% of that in the control. Moreover, this inhibition was blocked by treatment with mifepristone, a glucocorticoid receptor (GR) antagonist, but not by spironolactone, a mineralocorticoid receptor (MR) antagonist. In an lactate dehydrogenase (LDH) assay, CORT did not show any cytotoxic effect on RAW264.7 cells. JC-1 cell staining also showed that CORT did not influence mitochondrial dysfunction in RAW264.7 cells. In an investigation of the modulation of a signaling cascade by CORT, treatment with CORT promoted the translocation of GR, but not MR, from the cytosol to the nucleus in RAW264.7 cells. In conclusion, our findings suggest that CORT suppresses the proliferation of RAW264.7 cells by controlling the transcription of a particular gene, which is related to cell proliferation, through the formation of a CORT-GR complex.Key words glucocorticoid; mineralocorticoid; corticosterone; RAW264.7; mifepristone; spironolactone Corticosterone (CORT), which is classified as a steroid hormone, is an adrenal corticosteroid that plays a role in a wide range of phenomena, such as the regulation of glucose metabolism, the reaction of the immune system and the stress response. CORT is one of the main corticosteroids in rodents. There are two types of adrenal corticosteroid receptors: type II, or glucocorticoid receptor (GR), and type I, or mineralocorticoid receptor (MR).1,2) It has been demonstrated that CORT has greater affinity for MR than for GR. 3,4) In general, both GR and MR are localized in the cytosol. It has been demonstrated that a ligand-steroid hormone receptor complex forms a homodimer together with another chaperon protein once CORT binds to steroid hormone receptor. After it forms a homodimer complex, this complex translocates from the cytosol to the nucleus and binds to a particular motif of DNA to regulate DNA transcription.5) In the case of GR, intracellular GR is inactivated by the formation of complexes with several proteins, such as heat-shock proteins.6,7) After the active ligand-steroid hormone receptor complex forms a homodimer and translocates to the nucleus from the cytosol, it modulates the transcriptional responses of inflammatory genes, either by binding directly to DNA or by cooperating with some other protein or signal cascade, such as nuclear facto...

show abstract

“…Glucocorticoids are known M2 polarizing stimuli and in a microarray study of glucocorticoid-responsive genes, the gene most significantly reduced in embryonic glucocorticoid receptor deficient mice is the M2 polarization-associated gene Chi3l3. 142 They are particularly associated with the M2a subset, which aside from Th2 responses is also linked to negative aspects including ECM production and allergy. 48,51 The effect of such medications on developmental macrophages requires examination to ascertain if inappropriate skewing of macrophage phenotype may contribute to some of the negative side effects of glucocorticoid treatment.…”

Section: Csf-1 and Macrophage Manipulation In Developmentmentioning

confidence: 99%

Macrophages and CSF-1

Jones¹,

Ricardo

2013

Organogenesis

127

View full text Add to dashboard Cite

Identification of glucocorticoid‐regulated genes that control cell proliferation during murine respiratory development

Cited by 46 publications

References 49 publications

Dynamic expression of chymotrypsin-like elastase 1 over the course of murine lung development

Dynamic expression of chymotrypsin-like elastase 1 over the course of murine lung development

Corticosterone Suppresses the Proliferation of RAW264.7 Macrophage Cells via Glucocorticoid, But Not Mineralocorticoid, Receptor

Macrophages and CSF-1

Contact Info

Product

Resources

About