Nerve growth factor promotes endothelial progenitor cell-mediated angiogenic responses.

Chandrakala S. Jadhao, Ashay Bhatwadekar, Youde Jiang, Michael E. Boulton, Jena J. Steinle, Maria B. Grant

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In response to ischemia, retinal neuronal cells express nerve growth factor (NGF), which can be proangiogenic. Endothelial progenitor cells (EPCs) can participate with the resident vasculature to promote angiogenesis. We postulated that NGF may stimulate CD34 + EPCs to convert to an angiogenic phenotype. Human CD34 + cells and human retinal endothelial cells (HRECs) were used to examine the effect of NGF on key steps associated with neovascularization. CD34 + cells and HRECs were stimulated with NGF (1 to 4 pM) for 24, 48, and 72 hours. Cell migration was measured using a modified Boyden chamber assay. Expression of the receptor for the cytokine stromal derived growth factor 1 (SDF-1), CXCR-4, was assessed by flow cytometry. In vitro angiogenesis was tested using a three-dimensional (3D) extracellular matrix with HRECs/CD34 + cell cocultures. NGF receptor activation was assessed by western analysis. NGF promoted proliferation of CD34 + cells but not HRECs. Pretreatment of CD34 + cells with NGF increased CXCR-4 expression in CD34 + cells, resulting in enhanced migration to SDF-1 (P <0.0001). The enhanced tubule-forming effect of NGF in HRECs was further potentiated by coculture with NGF-pretreated CD34 + cells (P <0.01). The beneficial effect of NGF was blocked (P <0.0001) by the ERK inhibitor PD98059. In both CD34 + and HRECs, NGF increased phosphorylation of neurotrophic tyrosine kinase receptor type 1 (TrkA) receptor by ERK1 activation (P <0.01). Our in vitro results suggest that NGF released from ischemic nerves in vivo may contribute to the "angiogenic switch" by stimulating the angiogenic behavior of CD34 + cells while minimally affecting resident retinal endothelial cells.

Original languageEnglish (US)
Pages (from-to)2030-2037
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number4
StatePublished - Apr 2012
Externally publishedYes

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Nerve Growth Factor
Endothelial Cells
trkA Receptor
Coculture Techniques
Intercellular Signaling Peptides and Proteins
Endothelial Progenitor Cells
Nerve Growth Factor Receptor
Cytokine Receptors
Cell Movement
Extracellular Matrix
Flow Cytometry
Ischemia
Phosphorylation
Cell Proliferation
Phenotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jadhao, C. S., Bhatwadekar, A., Jiang, Y., Boulton, M. E., Steinle, J. J., & Grant, M. B. (2012). Nerve growth factor promotes endothelial progenitor cell-mediated angiogenic responses. Investigative Ophthalmology and Visual Science, 53(4), 2030-2037.

Nerve growth factor promotes endothelial progenitor cell-mediated angiogenic responses. / Jadhao, Chandrakala S.; Bhatwadekar, Ashay; Jiang, Youde; Boulton, Michael E.; Steinle, Jena J.; Grant, Maria B.

In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 4, 04.2012, p. 2030-2037.

Research output: Contribution to journalArticle

Jadhao, CS, Bhatwadekar, A, Jiang, Y, Boulton, ME, Steinle, JJ & Grant, MB 2012, 'Nerve growth factor promotes endothelial progenitor cell-mediated angiogenic responses.', Investigative Ophthalmology and Visual Science, vol. 53, no. 4, pp. 2030-2037.
Jadhao, Chandrakala S. ; Bhatwadekar, Ashay ; Jiang, Youde ; Boulton, Michael E. ; Steinle, Jena J. ; Grant, Maria B. / Nerve growth factor promotes endothelial progenitor cell-mediated angiogenic responses. In: Investigative Ophthalmology and Visual Science. 2012 ; Vol. 53, No. 4. pp. 2030-2037.
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