scholarly journals Effects of miRNA-200b on the development of diabetic retinopathy by targeting VEGFA gene

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
En-Hui Li ◽  
Qin-Zhu Huang ◽  
Gao-Chun Li ◽  
Zhen-Yang Xiang ◽  
Xin Zhang

The present study explored the effect of miR-200b on the development of diabetic retinopathy (DR) by targeting vascular endothelial growth factor A (VEGFA) gene. The study populations consisted of 255 DR patients (case group) and 253 healthy people (control group), while the expressions of miR-200b and VEGFA mRNA were detected by quantitative real-time PCR (qRT-PCR). Bioinformatics software and dual-luciferase reporter assay were used to confirm VEGFA as a target gene of miR-200b. Also, a total of 70 Wistar male rats were selected and randomly assigned into blank, normal control (NC), miR-200b mimics, miR-200b inhibitors, miR-200b inhibitors + silencing vascular endothelial growth factor A (siVEGFA), and siVEGFA groups (n=10/group) respectively. Streptozotocin (STZ)-induced rat models of DR were successfully established. VEGFA, transforming growth factor-β1 (TGF-β1), hepatocyte growth factor (HGF), and pigment epithelium-derived factor (PEDF) were detected using qRT-PCR and Western blotting. In comparison with the control group, the case group showed lower expression of miR-200b but higher expression of VEGFA mRNA. VEGFA was confirmed as a target gene of miR-200b. Rats in the miR-200b mimics and siVEGFA groups exhibited higher expression of PEDF mRNA and protein but lower expressions of VEGFA, TGF-β1, HGF protein, and mRNA than the NC group. There was no remarkable difference in expressions of PEDF, VEGFA, TGF-β1, HGF protein, and mRNA between the miR-200b inhibitors + siVEGFA and NC groups. In conclusion, the present study demonstrated that miR-200b might alleviate DR development by down-regulating its target gene VEGFA.

2017 ◽  
Vol 14 (4-5) ◽  
pp. 66-70
Author(s):  
A A Lebedenko ◽  
T P Shkurat ◽  
E V Mashkina ◽  
O E Semernik ◽  
T K Dreyzina

The growth factors such as transforming growth factor β (TGF-β) and vascular endothelial growth factor (VEGF) are played a particular role in the pathogenesis of atopic dermatitis. Therefore, the study of the genetic aspects of their association with risk of atopic dermatitis development in children is of great practical and scientific interest. Background. To study the association of the Arg25Pro polymorphisms of the TGF-β gene and the C634G gene of the VEGF gene with the risk of atopic dermatitis in children. Methods. Allelic variants of Arg25Pro gene TGF-β1 and S634G VEGFA gene in children with atopic dermatitis were studied with method of allelespecific polymerase chain reaction. The control group consisted of patients I and Ila of the health groups of the corresponding sex and age. Results. The results of genetic studies have shown that the occurrence frequency of genotype polymorphism Arg25Pro TGF-β1 gene in patients did not have significant differences from control group (p>0,05). Moreover, among patients who are heterozygous for the gene Arg25Pro TGF-β1, significantly more often had moderate (77,78%) and severe (33,33%) of course of the disease. It is established that the relationship between inheritance of C and Gallele polymorphism C634G VEGFA gene and the development of atopic dermatitis is also statistically significant (χ2=0,33, p=0,57). Conclusion. The study of polymorphisms of Arg25Pro gene of TGF-β and C634G gene of VEGF did not reveal a significant relationship between their inheritance and development of atopic dermatitis in children.


Author(s):  
Mohammad Hossein Razi ◽  
Maryam Eftekhar ◽  
Nasrin Ghasemi ◽  
Mohammad Hasan Sheikhha ◽  
Ali Dehghani Firoozabadi

Background: Using blood-based biomarkers such as microRNAs (miRNAs) may allow particularly effective and minimally invasive diagnosis and treatment of endometriosis. Objective: We evaluated the differential expression of circulating miRNA-185-5p (miR- 185-5p), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) target genes between endometriosis and healthy women. Materials and Methods: 25 women with a history of endometriosis (grad III-IV) diagnosed by laparoscopy as the case group and 25 women without endometriosis underwent laparoscopy for ovarian cysts or pelvic pain as the control group were enrolled in this case-control study. Blood samples were obtained, and total RNA was used for high-throughput small RNA sequencing, and this was confirmed by means of quantitative real-time polymerase chain reaction (qRT-PCR). Results: miRNA expression profiling using non-coding RNA sequencing revealed that one miRNA including miR-185-5p was significantly down-regulated in the case group compared with the controls. The qRT-PCR results showed significant downregulation of the expression level of miR-185-5p (p < 0.01) in the plasma of the case group. Receiver operating characteristic (ROC) curve analysis showed the area of miR-185-5p under the ROC curve for endometriosis diagnosis was 0.919 (p < 0.001). The RT-PCR results demonstrated that there was no significant difference in the expression of VEGF and PDGF mRNA of blood samples in the cases compared to the control group (PDGF, p = 0.09 and VEGF, p = 0.36). Conclusion: The low expression of miR-185-5p in the plasma of women with endometriosis could be employed as an important non-invasive biomarker for early detection and screening of endometriosis by blood samples. Key words: Biomarker, miRNA, Diagnosis, Endometriosis, Angiogenesis.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22082-e22082
Author(s):  
Valeria A. Bandovkina ◽  
Elena M. Frantsiyants ◽  
Ludmila Ya. Rozenko ◽  
Viktoria V. Pozdnyakova ◽  
Natalia D. Cheryarina ◽  
...  

e22082 Background: Clusters of tumor cells in blood vessels secrete VEGF family factors necessary for the formation of premetastatic niches. TGF-β activates the epidermal-mesenchymal transition (EMT). The purpose of the study was to analyze levels of angiogenesis and EMT factors in the blood of patients with cutaneous melanoma (M) and chronic neurogenic pain (CNP). Methods: Blood levels of VEGF-A, VEGF-C, VEGFR-1, VEGFR-3, TGF-β1 and TGF-βR2 were measured by ELISA in patients with Т3-4NxM0 melanoma: 21 women with CNP (pelvic pain - 7, osteochondrosis – 14), mean age 67.2±2.7 years; 17 men with CNP (osteochondrosis), mean age 65.6±3.1 years. The control group included patients with melanoma similar in age, gender and disease stages without CNP. Results: VEGF-A in women and men with M+CNP was higher than in controls by 2.7 and 24.9 times respectively; VEGFR-1 was decreased in women by 1.8 times and increased in men by 1.8 times. VEGF-С was unchanged in women and 1.5 times higher in men, and VEGFR-3 was increased by 2.2 times in women and unchanged in men. TGF-β1 was elevated in women and men with M+CNP by 1.4 and 1.8 times, compared to controls, TGF-βR2 – by 1.9 and 2 times respectively. Conclusions: In the blood of women with M+CNP, CNP activates the blood vascular endothelial growth factor VEGF-A and the factor of epidermal-mesenchymal transition TGF-β, while in the blood of men with M+CNP it activates the blood vascular endothelial growth factor VEGF-A, the lymphatic vascular endothelial growth factor VEGF-C and the factor of epidermal-mesenchymal transition TGF-β. VEGF mediates vascular permeability and is associated with the mobilization of endothelial progenitor cells from the bone marrow into premetastatic niches. Activation of TGF-β signaling promotes the induction of the epidermal-mesenchymal transition and supports the properties of cancer stem cells.


Author(s):  
YanuarEka P. ◽  
Hendy Hendarto ◽  
Widjiati .

Retrograde menstruation lead to I Kappa B Kinase (IKK) fosforilation in peritoneum macrophage and cause secretion of proinflammatory cytokine interleukin1β then stimulate endometriosis cell to produce Vascular Endothelial Growth Factor which lead to increasing of endometriosis lession seen as endometriosis implant area. Cytokine secretion was inhibited through prevention of NF-κB activation by dragon red fruit rind extract (Hylocereuspolyrhizus). The aim of this reserach is to know the effect of dragon red fuit rind extract with 0,25; 0,5; and 1 mg/g bodyweight dosage toward IL-1β, VEGF expression and implant area in endometriosis mice model. The design of this experiment was randomized post test only control group design.Endometrios mice model were made in 14 days and split into two group, positive control group and treatment group after two week negative control group and postive control group were given Na-CMC 0,5% solution consequetively, and treatment group were given dragon red fruit extract with different dosage. Signification number for IL-1β is p>0,05, signification number for VEGF is p>0,05, and implant area signification number is p>0,05. Administration of dragon red fruit rind extract can decrease IL-1β, VEGF, and implant area.


2014 ◽  
Vol 58 (2) ◽  
pp. 255-260
Author(s):  
Aleksandra Sobczyńska-Rak ◽  
Izabela Polkowska ◽  
Adam Brodzki

Abstract The aim of the study was to determine the levels of the vascular endothelial growth factor (VEGF) in the serum of dogs suffering from splenic malignant tumours, prior to splenectomy, as well as three and six months after the surgery. Tumours and blood samples were collected from 10 dogs of various breeds, aged between 7 and 13 years, and from 10 control animals. Tumour sections were fixed in 10% buffered formalin for 24 h. The type of tumour was determined according to the WHO classification. Blood samples were centrifuged and the obtained sera were subjected to immunoenzymatic assays to determine the VEGF levels. The median of VEGF levels in the serum of dogs suffering from splenic malignant tumours was 37.85 pg/mL (15.40-107.18 pg/mL). The highest values were observed in dogs with confirmed metastases (107.18 pg/mL and 65.43 pg/mL). The VEGF values in control group were between 0.1 pg/mL and 13.04 pg/mL. A comparative analysis of the VEGF levels against the animals' survival time indicated that VEGF overexpression may serve as a prognostic factor in cases of malignant tumours of the spleen.


2021 ◽  
Vol 11 (5) ◽  
pp. 841-846
Author(s):  
Wei Li ◽  
Yufang Zhang ◽  
Fuping Li ◽  
Yufen Shi ◽  
Yan Wang

Polycystic ovary syndrome (PCOS) is a female endocrine disorder and frequently leads to infertility. Vascular endothelial growth factor (VEGF) has crucial roles and matrix metalloproteinase (MMPs) is correlated with cell migration. Both of them are involved in the occurrence and progression of PCOS. This study established a rat PCOS model using letrozole to measure the expression of VEGF, MMP-2 and MMP-9 (MMP-2/9), to analyze its correlation with PCOS. Letrozole was applied by gavage to establish rat PCOS model. General condition and ovarian tissue morphology were observed under a light field microscope. ELISA and immunohistochemistry (IHC) were used to detect serum or tissue expression of VEGF, MMP-2/9. Estrous cycle of rats was disrupted after 12 d for using letrozole. Vaginal smear showed abundant leukocytes with sparse keratinocytes. Ovary showed whitening and increased volume, with early phase small follicles plus lower granular cells or corpus luteum. Compared to control group, experimental group had significantly higher VEGF, MMP-2/9 (P < 0.05), which were higher in antral follicles than those in preantral follicle with higher expressions than primordial follicle (P < 0.05). In conclusion, VEGF, MMP-2/9 are abundantly expressed in both serum and tissues of PCOS rats.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Alexandra H Smith ◽  
Michael A Kuliszewski ◽  
Hiroko Fujii ◽  
Duncan J Stewart ◽  
Jonathan R Lindner ◽  
...  

We have previously shown that ultrasound-mediated (UM) delivery of vascular endothelial growth factor (VEGF) plasmid-bearing microbubbles promotes therapeutic angiogenesis. While VEGF is important during the initiation of angiogenesis, it results in primarily immature vessels, which are prone to late regression. Angiopoietin (Ang)-1 is a potent growth factor that acts to stabilize the neovasculature, later in the angiogenic process. We hypothesized that temporal delivery of VEGF and Ang-1 plasmid DNA would result in a more sustained angiogenic response, as compared to VEGF alone, in the setting of severe chronic ischemia. Methods : Unilateral hindlimb ischemia was produced by iliac artery ligation in 30 rats. At day 14 post-ligation, microvascular blood velocity (β) and flow (MBF) in the proximal hindlimb muscles were assessed by contrast-enhanced ultrasound (CEU). UM-delivery of plasmid (500 μg cDNA)-bearing microbubbles (1×109), was then performed at pre-specified time points, with treatment groups including VEGF alone at day 14; VEGF at day 14 followed by Ang-1 at day 28; and control rats receiving no therapy (n=10 per group). β and MBF were re-assessed at day 28 and 8 wks post-ligation. Results : Relative MBF (normalized to the contralateral normal leg) remained reduced at all time points after ligation in the control group. In VEGF-alone treated animals, MBF in the ischemic leg increased 2 wks after delivery (0.48 ± 0.19 to 0.82 ± 0.23, p < 0.001), but regressed over the next 4 wks (0.61 ± 0.14 at 8 wk, NS vs. 2 wks). In the VEGF/Ang-1 treated animals, MBF in the ischemic leg also increased 2 weeks after VEGF delivery (0.39 ± 0.19 to 0.69 ± 0.28, p < 0.01); however, vascular regression was prevented by late Ang1 delivery (0.83 ± 0.20 at 8 wks, p < 0.005 vs. 2 wks and p<0.01 vs VEGF alone at 8 wks). At week 8, relative β values were greater in VEGF/Ang-1 treated compared to VEGF-alone treated animals (0.87 ± 0.33 to 0.60 ± 0.23, p < 0.05). Conclusions : Compared to delivery of VEGF alone, delivery of Ang-1 plasmid DNA at 2 wks post-VEGF gene delivery results in sustained improvement in MBF, with prevention of late vascular regression. The greater microvascular blood velocity in VEGF/Ang-1 treated muscle may signify improved vascular functionality with late Ang-1 therapy.


2018 ◽  
Vol 9 ◽  
pp. 204173141880863 ◽  
Author(s):  
Qiang Chang ◽  
Junrong Cai ◽  
Ying Wang ◽  
Ruijia Yang ◽  
Malcolm Xing ◽  
...  

Soft tissue generation, especially in large tissue, is a major challenge in reconstructive surgery to treat congenital deformities, posttraumatic repair, and cancer rehabilitation. The concern is along with the donor site morbidity, donor tissue shortage, and flap necrosis. Here, we report a dissection-free adipose tissue chamber–based novel guided adipose tissue regeneration strategy in a bioreactor of elastic gelatin cryogel and polydopamine-assisted platelet immobilization intended to improve angiogenesis and generate large adipose tissue in situ. In order to have matched tissue mechanics, we used 5% gelatin cryogel as growth substrate of bioreactor. Platelets from the platelet-rich plasma were then immobilized onto the gelatin cryogel with the aid of polydopamine to form a biomimetic bioreactor (polydopamine/gelatin cryogel/platelet). Platelets on the substrate led to a sustained high release in both platelet-derived growth factor and vascular endothelial growth factor compared with non-polydopamine-assisted group. The formed bioreactor was then transferred to a tissue engineering chamber and then inserted above inguinal fat pad of rats without flap dissection. This integrate strategy significantly boomed the vessel density, stimulated cellular proliferation, and upregulated macrophage infiltration. There was a noticeable rise in the expression of dual-angiogenic growth factors (platelet-derived growth factor and vascular endothelial growth factor) in chamber fluid; host cell migration and host fibrous protein secretion coordinated with gelatin cryogel degradation. The regenerated adipose tissue volume gained threefold larger than control group (p < 0.05) with less fibrosis tissue. These results indicate that a big well-vascularized three-dimensional mature adipose tissue can be regenerated using elastic gel, polydopamine, platelets, and small fat tissue.


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