Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels

Jacobo, Sarah Melissa P; Kazlauskas, Andrius

doi:10.1074/jbc.m114.634154

Cited by 62 publications

(42 citation statements)

References 54 publications

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“…IGF1 promotes migration and tube formation in ECs, 28 and stabilizes neovessels generated from ECs through extracellular signal-regulated kinase activation. 29 CTGF plays a central role in diseases in which tissue Inhibiting Ninj1 expression in cECs had no effect on their ability to form tube-like structures; however, Ninj1 overexpression decreased EC tube formation. This discrepancy between the loss-and gain-of function phenotypes could be due, in part, to a low expression level of endogenous Ninj1 in cECs under normal conditions.…”

Section: Discussionmentioning

confidence: 99%

Ninjurin1 Is a Novel Factor to Regulate Angiogenesis Through the Function of Pericytes

Matsuki

Kabara

Saito

et al. 2015

Circ J

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Background: Capillary pericytes (cPCs), the mural cells of microvessels, play an important role in the formation and maintenance of microvessels; however, little is known about the mechanisms of how cPCs regulate angiogenesis. To identify factors that modulate cPC function, genes whose levels were altered in cPCs during neovessel formation were identified through a microarray screen. Methods and Results:Ninjurin1 (nerve injury-induced protein, Ninj1) was selected as a candidate factor for angiogenesis regulation. Ninj1 was expressed in capillary cells including endothelial cells (cECs) and was expressed at a higher level in cPCs. Hypoxia induced the gene expression of Ninj1 in addition of vascular endothelial growth factor (VEGF) in cPCs. When cPCs were co-incubated with a thoracic aorta in a three-dimensional Matrigel system, the length of the EC-tubes sprouting from the aorta was increased. Small interfering RNA-mediated downregulation of Ninj1 in cPCs enhanced these cPCs-mediated angiogenic effects, whereas overexpression of Ninj1 attenuated their effects. The production of angiogenic growth factors, such as VEGF and angiopoietin 1, by cPCs was enhanced by the downregulation of Ninj1, and reduced by the overexpression of Ninj1. also determined. EC Tube Formation Angiogenesis AssayThe EC tube formation assay was performed as previously described. 14 A 40-μl volume of growth factor-reduced Matirgel was added to each well of a 96-well plate at room temperature. The gel was solidified at 37°C for at least 30 min and then seeded with 1×10 4 cells/well in 100 μl medium (EBM2 with 2% FBS and 10 ng/ml VEGF). The assay was performed in a CO2 incubator, with plates incubated at 37°C for 24 h. Images were obtained by phase contrast microscopy and the length of the tube-like structure in each well was measured at 40× magnification. Hind Limb Ischmia Surgery and ImmunocytochemistryMale C57BL/6 mice 12 weeks of age were used for experiments. All animal protocols were approved by the Animal Care and Use Committee of Asahikawa Medical University. Unilateral hindlimb ischemia (HLI) models were established by ligation and excision of the femoral artery/vein as previously described. 16 At predetermined time points, mice were sacrificed by overdose with a pentobarbital-based euthanasia solution (200 mg/kg by intraperitoneal injection). Gastrocnemius muscle samples were collected and stored at −80°C for quantitative polymerase chain reaction (qPCR) analysis. The histological assessment of ischemic limb tissue was performed 14 days after hindlimb surgery. Functional vessels were stained by injecting 300 μl phosphate-buffered saline (PBS) containing rhodamine-labeled G. simplicifolia lectin I (100 μg/ml, Vector Laboratories) via the tail vein. After 5 min, mice were sacrificed and perfused through the heart with PBS followed by 4% paraformaldehyde in PBS, and the gastrocnemius muscle was dissected and embedded in Tissue-Tek OCT medium. Ninj1 expression in 10-μm cross-sections was detected by immunocytochemistry using an anti-Ninj1 ...

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Section: Discussionmentioning

confidence: 99%

Ninjurin1 Is a Novel Factor to Regulate Angiogenesis Through the Function of Pericytes

Matsuki

Kabara

Saito

et al. 2015

Circ J

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“…7 Although the nature of the inhibitory factor expression involved in the avascularity of the fovea throughout life has yet to be clarified, 8 expression of several angiostatic proteins including ephrins A1 and A4 and their receptor EphA6, brain natriuretic peptide (BNP), and pigment epithelium-derived factor (PEDF) 1,[7][8][9][10] was associated with avascularity. In particular, the critical balance between the angiogenic VEGF and the angiostatic PEDF appears to be essential for preserving 11 and stabilizing 5,12,13 the avascular environment of the outer retina. There have been no reports to date on the differential expression of PEDF or other angiostatic factors involved in the development and persistence of the FAZ.…”

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confidence: 99%

Is Angiostatin Involved in Physiological Foveal Avascularity?

Böhm

Hodes

Brockhaus

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The primate central retina is characterized by an avascular fovea and well-defined perifoveal capillary plexus. Neither blood vessels nor their accompanying astrocytes enter the fovea during any stage of retinal development; a balance of angiogenic and angiostatic factors probably maintains foveal avascularity throughout life. The aim of this study was to identify potentially angiorepulsive factors involved in the development of the avascular primate retinal fovea. METHODS.Retinas of newborn, juvenile, and adult Callithrix jacchus and Macaca fascicularis monkeys and control human retinas were studied to determine the localization of angiostatin relative to III b-tubulin, glial fibrillary acidic protein, vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM), and the angiostatin receptor avb3-integrin in the foveal, macular, and peripheral retina. Expression studies were performed using immunohistochemistry (IHC) on retinal whole-mount and paraffin sections, and Western blotting on frozen material. The complex network of the main retinal cell types was identified by IHC of retinal whole mounts. RESULTS.In general, lifetime expression of angiostatin was found in all retinas. Colabeling with different markers revealed retinal ganglion cells as the main source of angiostatin expression in the primate retina, whereas PECAM-immunopositive blood capillaries expressed the angiostatin receptor avb3-integrin, and capillary-associated astrocytes expressed VEGF.CONCLUSIONS. This study provides the first evidence of angiostatin expression in the primate retina; the expression of angiostatin in the avascular foveal region and the peripheral retina suggests that angiostatin may play a role in the regulation of retinal vascularization, providing a possible explanation for the development and persistence of an avascular fovea.

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“…IGF-1 stimulates angiogenesis in vitro and in vivo [72–74]. Su et al [72] showed induced EC migration and capillary formation in an aorta ring assay, and Jacobo et al [73] recently demonstrated a role of this factor in stabilizing neovessels. In addition, sustained IGF-1 expression through gene delivery improves cardiac function in a myocardial infarction model [74].…”

Section: Discussionmentioning

confidence: 99%

“…Due to the complexity of the signaling pathways involved in the formation of stable vasculature, it is challenging to hypothesize what specific factor(s) might have promoted these effects. Improved cell survival in the condition with particles might have allowed the release of more angiogenic factors such as VEGF, TGF-β and IGF-1 by hMSC, which have been associated with improved vessel stabilization [73,77]. In addition, implanted hMSC may have contributed as mural cells [24].…”

Section: Discussionmentioning

confidence: 99%

PEG hydrogel containing calcium-releasing particles and mesenchymal stromal cells promote vessel maturation

et al. 2018

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Increasing blood vessel formation in diseased tissues with poor vascularization is a current clinical challenge. Cell therapy using human mesenchymal stem cells has received considerable interest, but low cell survival has hampered its translation to the clinic. Bioglasses and glass-ceramics have been explored as therapeutic agents for stimulating angiogenesis in soft tissues, but these effects need further evaluation in vivo. By incorporating both human mesenchymal stem cells and glass-ceramic particles in an implantable hydrogel, this study provides insights into the vasculogenic potential in soft tissues of the combined strategies. Enhancement of vessel formation and maturation supports further investigation of this strategy.

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Insulin-like Growth Factor 1 (IGF-1) Stabilizes Nascent Blood Vessels

Cited by 62 publications

References 54 publications

Ninjurin1 Is a Novel Factor to Regulate Angiogenesis Through the Function of Pericytes

Ninjurin1 Is a Novel Factor to Regulate Angiogenesis Through the Function of Pericytes

Is Angiostatin Involved in Physiological Foveal Avascularity?

PEG hydrogel containing calcium-releasing particles and mesenchymal stromal cells promote vessel maturation

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