Abstract
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.
Highlights
Intrauterine adhesions (IUA), identified as Asherman’s syndrome, are caused by the abnormal healing of the injured endometrial basal layer owing to a consequence of trauma or infection to the endometrium, and the clinical symptoms of IUA include menstrual disturbance, cyclical abdominal pain, infertility, and recurrent pregnancy loss [1,2]
The mRNA and protein expression of kinase-insert domain-containing receptor (KDR) was statistically higher in the endometrium of IUA patients than that of controls, and the expression levels were positively correlated to the severity of IUA
Cassidy et al [21] observed that the KDR mRNA levels in the peritoneal adhesion tissue were reduced by nearly 50% after a single intraoperative dose of valproic acid (VPA), with the reduction of adhesiogenic substrates extravasating into the peritoneum, thereby providing a new perspective for the clinical prevention and treatment of adhesions
Summary
Intrauterine adhesions (IUA), identified as Asherman’s syndrome, are caused by the abnormal healing of the injured endometrial basal layer owing to a consequence of trauma or infection to the endometrium, and the clinical symptoms of IUA include menstrual disturbance (amenorrhea/hypomenorrhea), cyclical abdominal pain, infertility, and recurrent pregnancy loss [1,2]. IUA as a fibrosis-induced disease can provide a good perspective for finding a new therapy. Vascular endothelial growth factor receptors (VEGFRs), a series of transmembrane receptor tyrosine kinases, could bind VEGF to initiate a signaling cascade that culminates in cellular migration, mitosis, and proliferation, thereby promoting angiogenesis and inducing fibrosis of endometrium [7]. KDR can promote mitosis, increase vascular permeability, and is involved in the induction of angiogenesis [11].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
