scholarly journals Decision letter: Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly

2016 ◽  
Keyword(s):  
Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Heart Tube ◽  
Pdgf Signaling ◽  
Tube Assembly

scholarly journals Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Joshua Bloomekatz ◽  
Reena Singh ◽  
Owen WJ Prall ◽  
Ariel C Dunn ◽  
Megan Vaughan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ectopic Expression ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Heart Tube ◽  
Cardiac Morphogenesis ◽  
Factor Receptor Alpha ◽  
Pdgf Signaling ◽  
Tube Assembly ◽  
Cardiac Fusion

Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. Mutation of pdgfra disrupts heart tube assembly in both zebrafish and mouse. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish pdgfra mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline during cardiac fusion. Intriguingly, the ligand pdgfaa is expressed in the endoderm medial to the pdgfra-expressing myocardial precursors. Ectopic expression of pdgfaa interferes with cardiac fusion, consistent with an instructive role for PDGF signaling. Together, these data uncover a novel mechanism through which endodermal-myocardial communication can guide the cell movements that initiate cardiac morphogenesis.

scholarly journals PDGF signaling directs cardiomyocyte movement toward the midline during heart tube assembly

2016 ◽  
Author(s):  
Joshua Bloomekatz ◽  
Reena Singh ◽  
Owen W.J. Prall ◽  
Ariel C. Dunn ◽  
Megan Vaughan ◽  
...  
Keyword(s):  
Essential Role ◽  
Ectopic Expression ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Heart Tube ◽  
Cardiac Morphogenesis ◽  
Factor Receptor Alpha ◽  
Pdgf Signaling ◽  
Tube Assembly ◽  
Cardiac Fusion

AbstractCommunication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. In both zebrafish and mouse, mutation of pdgfra inhibits cardiac fusion and can lead to cardia bifida. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish pdgfra mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline. Intriguingly, the ligand pdgfaa is expressed in the endoderm medial to the pdgfra-expressing myocardial precursors. Ectopic expression of pdgfaa interferes with cardiac fusion, consistent with an instructive role for PDGF signaling. Together, these data uncover a novel mechanism through which endodermal-myocardial communication guides the cell movements that initiate cardiac morphogenesis.IMPACT STATEMENTStudies in zebrafish and mouse implicate the PDGF signaling pathway in the communication between the endoderm and the myocardium that drives medial myocardial movement and thereby initiates cardiac morphogenesis.

scholarly journals Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis

2005 ◽  
Vol 201 (6) ◽  
pp. 925-935 ◽  
Author(s):  
Amir Abdollahi ◽  
Minglun Li ◽  
Gong Ping ◽  
Christian Plathow ◽  
Sophie Domhan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Kinase Inhibitors ◽  
Platelet Derived Growth Factor ◽  
Growth Factor Signaling ◽  
Pdgf Receptor ◽  
Pdgf Signaling ◽  
Radiation Induced

Pulmonary fibrosis is the consequence of a variety of diseases with no satisfying treatment option. Therapy-induced fibrosis also limits the efficacy of chemotherapy and radiotherapy in numerous cancers. Here, we studied the potential of platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitors (RTKIs) to attenuate radiation-induced pulmonary fibrosis. Thoraces of C57BL/6 mice were irradiated (20 Gy), and mice were treated with three distinct PDGF RTKIs (SU9518, SU11657, or Imatinib). Irradiation was found to induce severe lung fibrosis resulting in dramatically reduced mouse survival. Treatment with PDGF RTKIs markedly attenuated the development of pulmonary fibrosis in excellent correlation with clinical, histological, and computed tomography results. Importantly, RTKIs also prolonged the life span of irradiated mice. We found that radiation up-regulated expression of PDGF (A–D) isoforms leading to phosphorylation of PDGF receptor, which was strongly inhibited by RTKIs. Our findings suggest a pivotal role of PDGF signaling in the pathogenesis of pulmonary fibrosis and indicate that inhibition of fibrogenesis, rather than inflammation, is critical to antifibrotic treatment. This study points the way to a potential new approach for treating idiopathic or therapy-related forms of lung fibrosis.

scholarly journals Overexpression of the Sis Oncogene in a Canine Osteosarcoma Cell Line

2002 ◽  
Vol 39 (3) ◽  
pp. 411-412 ◽  
Author(s):  
R. A. Levine
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Cell Line ◽  
Platelet Derived Growth Factor ◽  
Osteosarcoma Cell ◽  
3T3 Cells ◽  
Autocrine Loop ◽  
Canine Osteosarcoma ◽  
Pdgf Signaling ◽  
Transcriptional Target

Specific oncogenes that contribute to the pathogenesis of canine osteosarcoma (OS) have not been identified. In the process of characterizing four OS cell lines, we have found one cell line, CO8, that overexpresses the sis oncogene, which encodes the platelet-derived growth factor (PDGF)-α. The expression of an important downstream transcriptional target of the PDGF signaling pathway, c-myc, is also elevated fourfold. Conditioned medium from CO8 alone specifically induces tyrosine phosphorylation and therefore the activation of the PDGF-α and PDGF-β receptors on murine 3T3 cells. All of the canine OS lines tested contain PDGF receptors and therefore are capable of responding to PDGF. Given the importance of PDGF in promoting cell proliferation, migration, and cell survival, the activation of the sis oncogene and the resultant growth factor autocrine loop potentially contribute to the pathogenesis of a subset of canine osteosarcomas.

scholarly journals Triazolopyrimidine (Trapidil), a Platelet-Derived Growth Factor Antagonist, Inhibits Parathyroid Bone Disease in an Animal Model for Chronic Hyperparathyroidism

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2000-2007 ◽  
Author(s):  
Sutada Lotinun ◽  
Jean D. Sibonga ◽  
Russell T. Turner
Keyword(s):  
Growth Factor ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Disease ◽  
Platelet Derived Growth Factor ◽  
Ribonuclease Protection Assay ◽  
Mrna Levels ◽  
Pdgf Signaling ◽  
Novel Strategy ◽  
Ribonuclease Protection

Parathyroid bone disease in humans is caused by chronic hyperparathyroidism (HPT). Continuous infusion of PTH into rats results in histological changes similar to parathyroid bone disease, including increased bone formation, focal bone resorption, and severe peritrabecular fibrosis, whereas pulsatile PTH increases bone formation without skeletal abnormalities. Using a cDNA microarray with over 5000 genes, we identified an association between increased platelet-derived growth factor-A (PDGF-A) signaling and PTH-induced bone disease in rats. Verification of PDGF-A overexpression was accomplished with a ribonuclease protection assay. Using immunohistochemistry, PDGF-A peptide was localized to mast cells in PTH-treated rats. We also report a novel strategy for prevention of parathyroid bone disease using triazolopyrimidine (trapidil). Trapidil, an inhibitor of PDGF signaling, did not have any effect on indexes of bone turnover in normal rats. However, dramatic reductions in marrow fibrosis and bone resorption, but not bone formation, were observed in PTH-treated rats given trapidil. Also, trapidil antagonized the PTH-induced increases in mRNA levels for PDGF-A. These results suggest that PDGF signaling is important for the detrimental skeletal effects of HPT, and drugs that target the cytokine or its receptor might be useful in reducing or preventing parathyroid bone disease.

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