The role of KDR in intrauterine adhesions may involve the TGF-ß1/Smads signaling pathway

The aim of this study was to investigate the role of kinase-insert domain-containing receptor (KDR) in intrauterine adhesions (IUA) and its mechanism. The Case group consisted of 92 patients diagnosed with IUA, and the Control group included 86 patients with uterine septum who had normal endometrium verified with an uteroscope. In addition, 50 rats were randomly assigned into Control, Sham, Model, NC-siRNA, and KDR-siRNA groups. Rats in the Model, NC-siRNA, and KDR-siRNA groups were induced by uterine curettage and lipopolysaccharide (LPS) treatment to establish the IUA model. Then, immunohistochemistry was applied for detection of VEGF and KDR expression, HE staining was used for observation of the endometrial morphology and gland counting, Masson staining for measurement of the degree of endometrial fibrosis, and qRT-PCR and western blot for the expression of KDR, VEGF, MMP-9, as well as TGF-β1/Smads pathway-related proteins. Compared with the Control group, the mRNA and protein expressions of KDR were significantly higher in IUA endometrial tissues, and the expression of KDR was positively correlated to the severity of IUA. In addition, the injection of si-KDR increased the number of endometrial glands, reduced the area of fibrosis, inhibited mRNA and protein expression of KDR and VEGF, up-regulated the expression of MMP-9 and Smad7, and decreased the expression level of TGF-β1, p-Smad2, p-Smad3, and Smad4 in rats with IUA. Highly-expressed KDR was related to patients' severity of IUA, and silencing KDR may prevent the occurrence and development of IUA via TGF-β1/Smads signaling pathway and up-regulating the expression of MMP-9.

Radiation up-regulates the expression of VEGF in a canine oral melanoma cell line

To evaluate radiosensitivity and the effects of radiation on the expression of vascular endothelial growth factor (VEGF) and VEGF receptors in the canine oral melanoma cell line, TLM 1, cells were irradiated with doses of 0, 2, 4, 6, 8 and 10 Gray (Gy). Survival rates were then determined by a MTT assay, while vascular endothelial growth factor receptor (VEGFR)-1 and -2 expression was measured by flow cytometry and apoptotic cell death rates were investigated using an Annexin assay. Additionally, a commercially available canine VEGF ELISA kit was used to measure VEGF. Radiosensitivity was detected in TLM 1 cells, and mitotic and apoptotic cell death was found to occur in a radiation dose dependent manner. VEGF was secreted constitutively and significant up-regulation was observed in the 8 and 10 Gy irradiated cells. In addition, a minor portion of TLM 1 cells expressed vascular endothelial growth factor receptor (VEGFR)-1 intracellularly. VEGFR-2 was detected in the cytoplasm and was down-regulated following radiation with increasing dosages. In TLM 1 cells, apoptosis plays an important role in radiation induced cell death. It has also been suggested that the significantly higher VEGF production in the 8 and 10 Gy group could lead to tumour resistance.

Capillary network formation by endothelial cells differentiated from human bone marrow mesenchymal stem cells

Human bone marrow derived mesenchymal stem cells [HBMSCs] have the potential to differentiate into cells such as adipocyte, osteocyte, hepatocyte and endothelial cells. In this study, the differentiation of hBMSCs into endothelial like-cells was induced in presence of vascular endothelial growth factor [VEGF] and insulin-like growth factor [IGF-1]. The differentiated endothelial cells were examined for their ability to express VEGF receptor-2 [VEGFR2] and von willebrand factor [vWF]. Then the cells were adopted to grow and develop capillary network in a semisolid gel matrix in vitro. The capillary network formation in a well of 24-well plate was found to be 85% in presence of VEGF [50ng/ml] and IGF-1 [20ng/ml] of the culture media. These data may suggest that the expression of endothelial markers in endothelial like-cells derived from hBMSCs is associated with their ability to form capillaries

Differential Expression of Placenta Growth Factors and Their Receptors In the Normal and Pregnancy-Induced Hypertensive Human Placentas

Placental development requires extensive angiogenesis and the invasion of the maternal decidua by the trophoblasts. Adequate and organized interaction of vascular endothelial growth factors (VEGF), placenta growth factors (PlGF), and their receptors are essential for a normal development and function of the placenta. In this study, we evaluated the expressions of PlGFs and their receptors, mRNAs by Northern blotting, in situ hybridization and RT-PCR in the normal and pregnancy-induced hypertensive (PIH) placentas. The expression level of PlGF-2 mRNA was lower in the PIH placentas compared to control as assessed by Northern blotting and in situ hybridization. PlGF mRNA was mainly localized to the vasculosyncytial membrane of placental villi and villous stroma. The expression of PlGF receptor-1 (PlGFR-1) was significantly increased in the PIH placentas compared to the normal ones. These results suggest that the alteration of PlGF-2 and PlGFR-1 mRNA expressions in the placenta are related to the pathogenesis of PIH.