Expression of IGFBP-3 by human retinal endothelial cell cultures: IGFBP-3 involvement in growth inhibition and apoptosis

Polyxenie E. Spoerri, Sergio Caballero, Sylvia H. Wilson, Lynn C. Shaw, Maria B. Grant

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

PURPOSE. Growth hormone (GH), insulin-like growth factor (IGF), and somatostatin (SST) modulate each other's actions. SST analogues have been successfully used to treat proliferative diabetic retinopathy (PDR) that is unresponsive to laser therapy and to retard the progression of severe nonproliferative retinopathy to PDR. In this study, the endogenous expression of IGF-binding protein (IGFBP)-3 was examined in human retinal endothelial cells (HRECs), the direct effects of IGFBP-3 on HRECs were evaluated, and the possible involvement of IGFBP-3 in mediating the growth inhibitory effects of SST receptor (SSTR) agonists in HRECs was assessed. METHODS. The cellular localization of IGFBP-3 was examined with anti-IGFBP-3 and fluorescein-conjugated goat anti-rabbit IgG. HRECs were exposed to varying concentrations of human recombinant IGFBP-3, and growth inhibition was evaluated by thiazolyl blue (MTT) conversion. Apoptosis was examined using fluorochrome-annexin V staining. Conditioned media (CM) from SSTR2 agonist (L779976)- treated or SSTR3 agonist (L796778)-treated HRECs were analyzed by ELISA for changes in expression of IGFBP-3. RESULTS. HREC immunostaining showed cell surface and cytoplasmic IGFBP-3. Exogenous IGFBP-3 induced a dose-dependent inhibition of HREC proliferation and staining with fluorochrome-annexin V showed numerous apoptotic HRECs. HRECs exposed to the SSTR2 or SSTR3 agonists expressed IGFBP-3 in a concentration-dependent manner. CONCLUSIONS. Cultured HRECs expressed endogenous IGFBP-3. Exogenous administration of IGFBP-3-induced growth inhibition and apoptosis, supporting a regulatory role for IGFBP-3 in endothelial cells. SSTR agonists mediate their growth-inhibitory effect, in part, by increasing expression of IGFBP-3.

Original languageEnglish (US)
Pages (from-to)365-369
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume44
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

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Insulin-Like Growth Factor Binding Protein 3
Endothelial Cells
Cell Culture Techniques
Apoptosis
Growth
Annexin A5
Diabetic Retinopathy
Somatostatin
Fluorescent Dyes
Staining and Labeling
Somatostatin Receptors
Laser Therapy
Somatomedins
Conditioned Culture Medium
Fluorescein
Recombinant Proteins
Goats
Growth Hormone

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Expression of IGFBP-3 by human retinal endothelial cell cultures : IGFBP-3 involvement in growth inhibition and apoptosis. / Spoerri, Polyxenie E.; Caballero, Sergio; Wilson, Sylvia H.; Shaw, Lynn C.; Grant, Maria B.

In: Investigative Ophthalmology and Visual Science, Vol. 44, No. 1, 01.01.2003, p. 365-369.

Research output: Contribution to journalArticle

Spoerri, Polyxenie E. ; Caballero, Sergio ; Wilson, Sylvia H. ; Shaw, Lynn C. ; Grant, Maria B. / Expression of IGFBP-3 by human retinal endothelial cell cultures : IGFBP-3 involvement in growth inhibition and apoptosis. In: Investigative Ophthalmology and Visual Science. 2003 ; Vol. 44, No. 1. pp. 365-369.
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T1 - Expression of IGFBP-3 by human retinal endothelial cell cultures

T2 - IGFBP-3 involvement in growth inhibition and apoptosis

AU - Spoerri, Polyxenie E.

AU - Caballero, Sergio

AU - Wilson, Sylvia H.

AU - Shaw, Lynn C.

AU - Grant, Maria B.

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N2 - PURPOSE. Growth hormone (GH), insulin-like growth factor (IGF), and somatostatin (SST) modulate each other's actions. SST analogues have been successfully used to treat proliferative diabetic retinopathy (PDR) that is unresponsive to laser therapy and to retard the progression of severe nonproliferative retinopathy to PDR. In this study, the endogenous expression of IGF-binding protein (IGFBP)-3 was examined in human retinal endothelial cells (HRECs), the direct effects of IGFBP-3 on HRECs were evaluated, and the possible involvement of IGFBP-3 in mediating the growth inhibitory effects of SST receptor (SSTR) agonists in HRECs was assessed. METHODS. The cellular localization of IGFBP-3 was examined with anti-IGFBP-3 and fluorescein-conjugated goat anti-rabbit IgG. HRECs were exposed to varying concentrations of human recombinant IGFBP-3, and growth inhibition was evaluated by thiazolyl blue (MTT) conversion. Apoptosis was examined using fluorochrome-annexin V staining. Conditioned media (CM) from SSTR2 agonist (L779976)- treated or SSTR3 agonist (L796778)-treated HRECs were analyzed by ELISA for changes in expression of IGFBP-3. RESULTS. HREC immunostaining showed cell surface and cytoplasmic IGFBP-3. Exogenous IGFBP-3 induced a dose-dependent inhibition of HREC proliferation and staining with fluorochrome-annexin V showed numerous apoptotic HRECs. HRECs exposed to the SSTR2 or SSTR3 agonists expressed IGFBP-3 in a concentration-dependent manner. CONCLUSIONS. Cultured HRECs expressed endogenous IGFBP-3. Exogenous administration of IGFBP-3-induced growth inhibition and apoptosis, supporting a regulatory role for IGFBP-3 in endothelial cells. SSTR agonists mediate their growth-inhibitory effect, in part, by increasing expression of IGFBP-3.

AB - PURPOSE. Growth hormone (GH), insulin-like growth factor (IGF), and somatostatin (SST) modulate each other's actions. SST analogues have been successfully used to treat proliferative diabetic retinopathy (PDR) that is unresponsive to laser therapy and to retard the progression of severe nonproliferative retinopathy to PDR. In this study, the endogenous expression of IGF-binding protein (IGFBP)-3 was examined in human retinal endothelial cells (HRECs), the direct effects of IGFBP-3 on HRECs were evaluated, and the possible involvement of IGFBP-3 in mediating the growth inhibitory effects of SST receptor (SSTR) agonists in HRECs was assessed. METHODS. The cellular localization of IGFBP-3 was examined with anti-IGFBP-3 and fluorescein-conjugated goat anti-rabbit IgG. HRECs were exposed to varying concentrations of human recombinant IGFBP-3, and growth inhibition was evaluated by thiazolyl blue (MTT) conversion. Apoptosis was examined using fluorochrome-annexin V staining. Conditioned media (CM) from SSTR2 agonist (L779976)- treated or SSTR3 agonist (L796778)-treated HRECs were analyzed by ELISA for changes in expression of IGFBP-3. RESULTS. HREC immunostaining showed cell surface and cytoplasmic IGFBP-3. Exogenous IGFBP-3 induced a dose-dependent inhibition of HREC proliferation and staining with fluorochrome-annexin V showed numerous apoptotic HRECs. HRECs exposed to the SSTR2 or SSTR3 agonists expressed IGFBP-3 in a concentration-dependent manner. CONCLUSIONS. Cultured HRECs expressed endogenous IGFBP-3. Exogenous administration of IGFBP-3-induced growth inhibition and apoptosis, supporting a regulatory role for IGFBP-3 in endothelial cells. SSTR agonists mediate their growth-inhibitory effect, in part, by increasing expression of IGFBP-3.

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