Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall.

By P. Lindblom, Holger Gerhardt, S. Liebner, A. Abramsson, M. Enge, Mats Hellstrom, G. Backstrőm, S. Fredriksson, U. Landegren, Henrik C Nystrom and 5 more. Genes & Development, 2003

682 citations recorded by the source corpus.

Several platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) family members display C-terminal protein motifs that confer retention of the secreted factors within the pericellular space. To address the role of PDGF-B retention in vivo, we deleted the retention motif by gene targeting in mice. This resulted in defective investment of pericytes in the microvessel wall and delayed formation of the renal glomerulus mesangium. Long-term effects of lack of PDGF-B retention included severe retinal deterioration, glomerulosclerosis, and proteinuria. We conclude that retention of PDGF-B in microvessels is essential for proper recruitment and organization of pericytes and for renal and retinal function in adult mice.

Subfields: Molecular Biology, Nephrology, Ophthalmology

View Paper: https://www.semanticscholar.org/paper/ff95af328df29067de69ecf15837fc7ba511af8d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Nephrology

J. Pouysségur

In Ophthalmology

Citations in the corpus

Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. (2011, background): “Targeted deletion of the retention motif in mice (pdgfb) leads to hypoplasia and partial detachment of pericytes (Lindblom et al., 2003), suggesting that PDGF-B needs to be presented as a cell surface or matrix-bound factor in order to exert a proper signal for pericyte recruitment to the vessel wal”
Targeting the tumour vasculature: insights from physiological angiogenesis (2010, background): “PDGF-BB is retained close to the endothelial cells through its carboxy-terminal retention motif that binds heparan sulphate proteoglycans in the ECM around the endothelial cells, stabilizing it as a guidance cue for pericyte”
The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction (2009, background): “Thus, endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall including the BBB [39].”
Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging (2010, background): “Much of the insight into brain pericyte biology arose from developmental studies and the analysis of pericyte-deficient transgenic mice with disrupted PDGF-B/PDGFRb signaling (Lindahl et al., 1997; Lindblom et al., 2003; Tallquist et al., 2003; Gaengel et al., 2009).”
Hypoxia signalling in cancer and approaches to enforce tumour regression (2006, background): “1b , Ang-1, through Tie-2 receptor tyrosine kinase signalling and platelet-derived growth factor-B (PDGF-B) action, induces pericyte recruitmen”
Role of platelet-derived growth factors in physiology and medicine. (2008, neutral): “Focal neovascular retinal disease resembling proliferative diabetic retinopathy has also been reported in two different mouse mutants with PDGF-B deficiency and accompanying loss of retinal pericytes (Enge et al. 2002; Lindblom et al. 2003).”
Diabetes and Wound Angiogenesis (2017, background): “In wounds, pericytes are actively recruited in response to several factors, with the best described being PDGF [52,53].”
The PDGF family: four gene products form five dimeric isoforms. (2004, background): “Genetic data from mice expressing only a non-matrix binding form of PDGF-B demonstrate the importance of the matrix association of these factors [44].”
The role of pericytes in blood-vessel formation and maintenance. (2005, background): “These mice are viable but have fewer pericytes, as they lack proper recruitment and integration of pericytes within the vessel wall, particularly in the retina and kidney (Lindblom et al., 2003).”
Central nervous system pericytes in health and disease (2011, background): “Genetic manipulations maintaining some residual PDGF-B and/or PDGFRβ activity lead to viable mouse models of pericyte deficienc”