NG2 Proteoglycan Expression by Pericytes in Pathological Microvasculature

Özerdem, Uğur; Monosov, Edward; Stallcup, William B.

doi:10.1006/mvre.2001.2376

Cited by 152 publications

(175 citation statements)

References 16 publications

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“…Moreover, immunostaining for NG2, a pericyte marker, 23 was reduced in imatinib-treated wounds. Similarly distended microvessels have been recorded in PDGFR-␤ and PDGF-B chain knockout mice 14,36 with subsequent studies confirming that these microaneurysms were caused by a failure to adequately recruit pericytes to nascent capillaries.…”

Section: Discussionmentioning

confidence: 98%

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Platelet-Derived Growth Factor-β Receptor Activation Is Essential for Fibroblast and Pericyte Recruitment during Cutaneous Wound Healing

Rajkumar

Boström

et al. 2006

The American Journal of Pathology

167

126

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Connective tissue remodeling provides mammals with a rapid mechanism to repair wounds after injury. Inappropriate activation of this reparative process leads to scarring and fibrosis. Here, we studied the effects of platelet-derived growth factor receptor-␤ blockade in vivo using the platelet-derived growth factor receptor (PDGFR)-␤ inhibitor imatinib mesylate on tissue repair. After 7 days, healing of wounds was delayed with significantly reduced wound closure and concomitant reduction in myofibroblast frequency, expression of fibronectin ED-A, and collagen type I. Using a collagen type I transgenic reporter mouse, we showed that inhibiting PDGFR-␤ activation restricted the distribution of collagen-synthesizing cells to wound margins and dramatically reduced cell proliferation in vivo. By 14 days, treated wounds were fully closed. Blocking PDGFR-␤ signaling did not prevent the differentiation of myofibroblasts in vitro but potently inhibited fibroblast proliferation and migration. In addition, PDGFR-␤ inhibition in vivo was accompanied by abnormal microvascular morphogenesis reminiscent of that observed in PDGFR-␤ ؊/؊ mice with significantly reduced immunostaining of the pericyte marker NG2. Imatinib treatment also inhibited pericyte proliferation and migration in vitro. This study highlights the significance of PDGFR-␤ signaling for the recruitment, proliferation, and functional activities of fibroblasts and pericytes during the early phases of wound healing.

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Section: Discussionmentioning

confidence: 98%

“…NG2 is a membrane-spanning chondroitin sulfate proteoglycan that is expressed by microvascular pericytes. 23 Biotinylated and Texas Red-conjugated antibodies were obtained from Vector Laboratories (Burlingame, CA).…”

Section: Antibodiesmentioning

confidence: 99%

Platelet-Derived Growth Factor-β Receptor Activation Is Essential for Fibroblast and Pericyte Recruitment during Cutaneous Wound Healing

Rajkumar

Boström

et al. 2006

The American Journal of Pathology

167

126

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“…The pericyte identity was confirmed upon immunohistochemical analysis of the mutant vessels with the pericyte markers smooth muscle actin (SMA), chondroitin sulfate proteoglycan 4 (Cspg4/NG2), and Pdgfr␤ ( Fig. 6D-K ;Lindahl et al 1997;Ozerdem et al 2002;Makinen et al 2007). In addition, we determined that these blood-filled mutant vessels also abnormally express platelet markers such as fibrin and CD41 (Supplemental Fig.…”

Section: Lec Phenotype Is Plastic Genes and Development 3285mentioning

confidence: 90%

Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity

Johnson¹,

Dillard²,

Bałuk³

et al. 2008

Genes Dev.

297

302

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The activity of the homeobox gene Prox1 is necessary and sufficient for venous blood endothelial cells (BECs) to acquire a lymphatic endothelial cell (LEC) fate. We determined that the differentiated LEC phenotype is a plastic, reprogrammable condition that depends on constant Prox1 activity for its maintenance. We show that conditional down-regulation of Prox1 during embryonic, postnatal, or adult stages is sufficient to reprogram LECs into BECs. Consequently, the identity of the mutant lymphatic vessels is also partially reprogrammed as they acquire some features typical of the blood vasculature. siRNA-mediated down-regulation of Prox1 in LECs in culture demonstrates that reprogramming of LECs into BECs is a Prox1-dependent, cell-autonomous process. We propose that Prox1 acts as a binary switch that suppresses BEC identity and promotes and maintains LEC identity; switching off Prox1 activity is sufficient to initiate a reprogramming cascade leading to the dedifferentiation of LECs into BECs. Therefore, LECs are one of the few differentiated cell types that require constant expression of a certain gene to maintain their phenotypic identity.[Keywords: Lymphatic endothelial cells; blood endothelial cells; lymphangiogenesis; reprogramming; Prox1; siRNA] Supplemental material is available at http://www.genesdev.org.

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“…Recently NG2 (neuron-glia antigen 2), the rat homologue of the Human Melanoma Proteoglycan (HMP), has been characterized as a pericyte maker (Ozerdem et al, 2001;Ozerdem et al, 2002). In quiescent rat mesenteric tissues NG2 labeling identifies smooth muscle cells along arterioles and vascular pericytes along all capillary vessels, yet not by smooth muscle cells along venules (Murfee et al, 2005).…”

Section: Role For Perivascular Cells In Hypertensionmentioning

confidence: 99%

Chapter 12 Structure of Microvascular Networks in Genetic Hypertension

Murfee

Schmid‐Schönbein

2008

Methods in Enzymology

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Microvascular rarefaction, defined by a loss of terminal arterioles, small venules and/or capillaries, is a common characteristic of the hypertension syndrome. While rarefaction has been associated with vessel specific free radical production, deficient leukocyte adhesion, and cellular apoptosis, the relationships of rarefaction with structural alterations at the network and cellular level remain largely unexplored. The objective of this study was to examine the architecture and perivascular cell phenotypes along microvascular networks in hypertensive versus normotensive controls in the context of imbalanced angiogenesis. Mesenteric tissues from age-matched adult male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were harvested and immnolabeled for PECAM and neuron-glia antigen 2 (NG2). Evaluation of intact rat mesenteric microvascular networks rats suggests that network alterations associated with hypertension are more complex than just a loss of vessels. Typical SHR versus WKY networks demonstrate a reduced branching architecture marked by more proximal arteriole/venous anastomoses and an absence of NG2 labeling along arterioles. Although less frequent, larger SHR microvascular networks display regions of dramatically increased vascular density. SHR and WKY lymphatic networks demonstrate increased vessel diameters and vascular density compared to networks in normotensive Wistar rats (the strain from which both the SHR and WKY originated). These observations provide a rationale for investigating the presence of local angiogenic factors and response of microvascular networks to therapies aimed at reversing rarefaction in genetic hypertension.

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NG2 Proteoglycan Expression by Pericytes in Pathological Microvasculature

Cited by 152 publications

References 16 publications

Platelet-Derived Growth Factor-β Receptor Activation Is Essential for Fibroblast and Pericyte Recruitment during Cutaneous Wound Healing

Platelet-Derived Growth Factor-β Receptor Activation Is Essential for Fibroblast and Pericyte Recruitment during Cutaneous Wound Healing

Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity

Chapter 12 Structure of Microvascular Networks in Genetic Hypertension

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