Expression of thrombospondin-1 in ischemia-induced retinal neovascularization.

Abstract

Thrombospondin-1 is an extracellular matrix protein that inhibits endothelial cell proliferation, migration, and angiogenesis. This study was performed to investigate the role of thrombospondin-1 in ischemic retinal neovascularization. In a murine model of retinal neovascularization, thrombospondin-1 mRNA was increased from postnatal day 13 (P13), with a threefold peak response observed on P15, corresponding to the time of development of retinal neovascularization. Prominent expression of thrombospondin-1 was observed in neovascular cells, specifically, cells adjacent to the area of nonperfusion. It has been suggested that vascular endothelial growth factor (VEGF) plays a major role in ischemia-induced retinal neovascularization of this model, so we studied the effects of VEGF on thrombospondin-1 expression. In bovine retinal microcapillary endothelial cells, VEGF induced a biphasic response of thrombospondin-1 expression; VEGF decreased thrombospondin-1 mRNA 0.41-fold after 4 hours, whereas it increased, with a threefold peak response, after 24 hours. VEGF-induced endothelial cell proliferation was completely inhibited by exogenous thrombospondin-1 and increased by 37.5% with anti-thrombospondin-1 antibody. The present findings suggest that, in the ischemic retina, retinal neovascular cells increase thrombospondin-1 expression, and VEGF may stimulate endogenous thrombospondin-1 induction, which inhibits endothelial cell growth. VEGF-mediated thrombospondin-1 induction in ischemia-induced angiogenesis may be a negative feedback mechanism.

• Authors: K Suzuma, H Takagi, A Otani, H Oh, Y Honda
• Journal: The American journal of pathology (Am J Pathol) Vol. 154 Issue 2 Pg. 343-54 (Feb 1999) ISSN: 0002-9440 [Print] United States
• PMID: 10027393 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelial Growth Factors
• Lymphokines
• RNA, Messenger
• Thrombospondin 1
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors
• Cycloheximide

Topics

• Animals
• Animals, Newborn
• Cattle
• Cells, Cultured
• Cycloheximide (pharmacology)
• Disease Models, Animal
• Endothelial Growth Factors (pharmacology)
• Endothelium, Vascular (drug effects, metabolism, pathology)
• Female
• Humans
• Infant, Newborn
• Ischemia (metabolism, pathology)
• Lymphokines (pharmacology)
• Mice
• Mice, Inbred C57BL
• Pregnancy
• RNA, Messenger (biosynthesis)
• Rats
• Retinal Neovascularization (etiology, metabolism, pathology)
• Retinal Vessels (drug effects, metabolism, pathology)
• Retinopathy of Prematurity (etiology, metabolism, pathology)
• Thrombospondin 1 (genetics, metabolism)
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors