Altered decorin leads to disrupted endothelial cell function: A possible mechanism in the pathogenesis of fetal growth restriction?

Abstract

Reduction of DCN in vascular endothelial cells leads to disrupted cell functions. The targets of DCN include genes that play important roles in angiogenesis and cellular growth. Therefore, differential expression of these may contribute to the pathogenesis of FGR and disease states in other microvascular circulations.

Antiangiogenic effects of decorin restored by unfractionated, low molecular weight, and nonanticoagulant heparins

“…[20][21][22][23][24][25] In our previous work, we showed that the messenger RNA and protein expression of the proteoglycan decorin (DCN) was reduced in PE-and FGR-affected placentae compared with controls. [26][27][28] Furthermore, we also showed that downregulation of DCN in human microvascular endothelial cells resulted in decreased cell growth and proliferation, decreased network formation (angiogenesis), and a modest increase in thrombin generation. 26 We also demonstrated that DCN was downregulated in the first trimester in women who went on to develop growth-restricted infants, suggesting that there is both a temporal relationship and biologic plausibility for the association between reduced DCN expression and subsequent development of PE/FGR.…”

“…[26][27][28] Furthermore, we also showed that downregulation of DCN in human microvascular endothelial cells resulted in decreased cell growth and proliferation, decreased network formation (angiogenesis), and a modest increase in thrombin generation. 26 We also demonstrated that DCN was downregulated in the first trimester in women who went on to develop growth-restricted infants, suggesting that there is both a temporal relationship and biologic plausibility for the association between reduced DCN expression and subsequent development of PE/FGR. 29 The results from these studies have led to the opportunity to investigate whether the addition of heparin to these DCN-reduced microvascular endothelial cells may result in a reversal of adverse cell growth and angiogenesis, as well as an expected anticoagulation effect.…”

“…The DCN siRNAs showed no significant DNA sequence similarity to other genes in GenBank complementary DNA databases (data not shown). 26 TIME cells were grown in EGM-2 MV and transfected with DCN siRNAs using HiPerfect transfection reagent (Qiagen). Negative control (NC) siRNA consisted of a pool of enzyme-generated siRNA oligonucleotides that were not specific for any known human genes (AllStars Negative siRNA; Qiagen).…”

“…Negative control (NC) siRNA consisted of a pool of enzyme-generated siRNA oligonucleotides that were not specific for any known human genes (AllStars Negative siRNA; Qiagen). 26 The Mock control represented the cells in media only. The efficacies of the 4 siRNAs in downregulating DCN, and the subsequent selection of the 2 best siRNA as DCNS2 and DCNS3, are depicted in our previous published work.…”

“…The efficacies of the 4 siRNAs in downregulating DCN, and the subsequent selection of the 2 best siRNA as DCNS2 and DCNS3, are depicted in our previous published work. 26 …”