Localization of chondromodulin-I at the feto-maternal interface and its inhibitory actions on trophoblast invasion in vitro

Shigenori Miura,Jun Kondo,Kaori Mitsui,Chisa Shukunami,Yuji Hiraki

doi:10.1186/1471-2121-12-34

Abstract

BackgroundChondromodulin-I (ChM-I) is an anti-angiogenic glycoprotein that is specifically localized at the extracellular matrix of the avascular mesenchyme including cartilage and cardiac valves. In this study, we characterized the expression pattern of ChM-I during early pregnancy in mice in vivo and its effect on invasion of trophoblastic cells into Matrigel in vitro.ResultsNorthern blot analysis clearly indicated that ChM-I transcripts were expressed in the pregnant mouse uterus at 6.5-9.5 days post coitum. In situ hybridization and immunohistochemistry revealed that ChM-I was localized to the mature decidua surrounding the matrix metalloproteinase-9 (MMP-9)-expressing trophoblasts. Consistent with this observation, the expression of ChM-I mRNA was induced in decidualizing endometrial stromal cells in vitro, in response to estradiol and progesterone. Recombinant human ChM-I (rhChM-I) markedly inhibited the invasion through Matrigel as well as the chemotactic migration of rat Rcho-1 trophoblast cells in a manner independent of MMP activation.ConclusionsThis study demonstrates the inhibitory action of ChM-I on trophoblast migration and invasion, implying the potential role of the ChM-I expression in decidual cells for the regulated tissue remodeling and angiogenesis at feto-maternal interface.

Highlights

Chondromodulin-I (ChM-I) is an anti-angiogenic glycoprotein that is localized at the extracellular matrix of the avascular mesenchyme including cartilage and cardiac valves
Chondromodulin-I (ChM-I) is a naturally occurring anti-angiogenic glycoprotein that localizes to the avascular domains of mesenchymal tissues such as cartilage, cardiac valves, and the eye [1,2,3], where angiogenesis is strictly limited
Using both recombinant and adenovirally expressed ChM-I protein, we have demonstrated that ChM-I inhibits the migration, proliferation, and tube morphogenesis of cultured vascular endothelial cells, and suppresses tumor angiogenesis [4,5,6,7,8]

Summary

Introduction

Chondromodulin-I (ChM-I) is an anti-angiogenic glycoprotein that is localized at the extracellular matrix of the avascular mesenchyme including cartilage and cardiac valves. Chondromodulin-I (ChM-I) is a naturally occurring anti-angiogenic glycoprotein that localizes to the avascular domains of mesenchymal tissues such as cartilage, cardiac valves, and the eye [1,2,3], where angiogenesis is strictly limited. Using both recombinant and adenovirally expressed ChM-I protein, we have demonstrated that ChM-I inhibits the migration, proliferation, and tube morphogenesis of cultured vascular endothelial cells, and suppresses tumor angiogenesis [4,5,6,7,8]. ChM-I-deficient mice show a vascularized phenotype in their aged cardiac valves, which is caused by a loss of anti-angiogenic valvular functions and abnormal vascular invasion [2] These studies suggest that ChM-I may serve as a matrix component that confers antiangiogenic resistance to specific mesenchymal tissues. ChM-I transcripts were detected in cardiac valve precursor cells of the heart at 9.5 days post coitum (p.c.) and its expression persisted in cardiac valves in the adult [2]

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