Role of platelet-derived growth factors in physiology and medicine.
TLDR
Basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts are reviewed.Abstract:
Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) have served as prototypes for growth factor and receptor tyrosine kinase function for more than 25 years. Studies of PDGFs and PDGFRs in animal development have revealed roles for PDGFR-alpha signaling in gastrulation and in the development of the cranial and cardiac neural crest, gonads, lung, intestine, skin, CNS, and skeleton. Similarly, roles for PDGFR-beta signaling have been established in blood vessel formation and early hematopoiesis. PDGF signaling is implicated in a range of diseases. Autocrine activation of PDGF signaling pathways is involved in certain gliomas, sarcomas, and leukemias. Paracrine PDGF signaling is commonly observed in epithelial cancers, where it triggers stromal recruitment and may be involved in epithelial-mesenchymal transition, thereby affecting tumor growth, angiogenesis, invasion, and metastasis. PDGFs drive pathological mesenchymal responses in vascular disorders such as atherosclerosis, restenosis, pulmonary hypertension, and retinal diseases, as well as in fibrotic diseases, including pulmonary fibrosis, liver cirrhosis, scleroderma, glomerulosclerosis, and cardiac fibrosis. We review basic aspects of the PDGF ligands and receptors, their developmental and pathological functions, principles of their pharmacological inhibition, and results using PDGF pathway-inhibitory or stimulatory drugs in preclinical and clinical contexts.read more
Citations
More filters
Journal ArticleDOI
Pericytes: developmental, physiological, and pathological perspectives, problems, and promises.
TL;DR: The history of investigations into pericytes, the mural cells of blood microvessels, are reviewed, emerging concepts are indicated, and problems and promise are pointed out.
Journal ArticleDOI
Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle.
TL;DR: It is suggested that interaction between muscle cells and PDGFRα+ mesenchymal progenitors, not the fate decision of satellite cells, has a considerable impact on muscle homeostasis and is the major contributor to ectopic fat cell formation in skeletal muscle.
Journal ArticleDOI
Vascularization is the key challenge in tissue engineering
TL;DR: Prevascularization techniques are compared to approaches in which biomolecules, such as growth factors, cytokines, peptides and proteins as well as cells are applied to generate new vessels to create vascularized tissues in vitro.
Journal ArticleDOI
Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition
Jason R. Rock,Christina E. Barkauskas,Michael J. Cronce,Yan Xue,Jeffrey R. Harris,Jiurong Liang,Paul W. Noble,Brigid L.M. Hogan +7 more
TL;DR: A previously unappreciated heterogeneity of cell types proliferating in fibrotic lesions is shown and pericytes and two epithelial cell populations are excluded as the origin of myofibroblasts.
Journal ArticleDOI
Tumor angiogenesis and vascular normalization: alternative therapeutic targets.
Claire Viallard,Bruno Larrivée +1 more
TL;DR: Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments.
References
More filters
Journal ArticleDOI
The hallmarks of cancer.
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
Journal ArticleDOI
The pathogenesis of atherosclerosis: a perspective for the 1990s
TL;DR: The ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.
Journal ArticleDOI
The biology of VEGF and its receptors.
TL;DR: Vascular endothelial growth factor (VEGF) is a key regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions and is implicated in pathologicalAngiogenesis associated with tumors, intraocular neovascular disorders and other conditions.
Journal ArticleDOI
Inflammation, Atherosclerosis, and Coronary Artery Disease
TL;DR: The evidence is recounted that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree.
Journal ArticleDOI
Inositol trisphosphate and calcium signalling
TL;DR: Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals through receptors whose molecular and physiological properties closely resemble the calcium-mobilizing ryanodine receptors of muscle.