Phosphatase and Tensin Homology Deletion Gene (PTEN) Regulates Fibroblast Precursor Cells Autophagy and Vascular Endothelial Growth Factor Signaling in Preeclampsia

2022 ◽  
Vol 12 (5) ◽  
pp. 1040-1045
Author(s):  
Jingfang Zhu ◽  
Jianglin Hu

Preeclampsia (PE) causes serious harm to the health of mothers and infants. PTEN regulates cell biological behaviors, but its role in preeclampsia have not been reported. Real time PCR and Western blot detected PTEN level in the placenta of PE patients and controls. Placental trophoblastderived cell line HTR8 was assigned into NC group, PTEN group and si-PTEN inhibitor group followed by measuring PTEN level, cell proliferation by MTT assay, cell invasion by Transwell, Caspase 3 activity, Beclin-1 and Atg-5 expression as well as PI3K/Akt/HIF-1α/VEGF signaling protein by Western blot. PTEN in PE patients was significantly downregulated (P < 0.05). Transfection of PTEN siRNA significantly down-regulated PTEN, promoted cell proliferation and invasion, reduced Caspase 3 activity, increased Beclin-1 and Atg-5, and PI3K/Akt/HIF-1α/VEGF protein expression (P < 0.05). Transfection of pcDNA 3.0-PTEN up-regulated PTEN and significantly reversed the above changes (P < 0.05). In conclusion, PTEN is reduced in PE and it can regulate pre-eclampsia trophoblast autophagy possibly through PI3K/Akt/HIF-1α/VEGF signaling, suggesting that PTEN can be a potential target for PE therapy.

2021 ◽  
Vol 9 ◽  
Author(s):  
Aniket Ramshekar ◽  
M. Elizabeth Hartnett

Retinopathy of prematurity (ROP) is a leading cause of blindness in children worldwide. Blindness can occur from retinal detachment caused by pathologic retinal angiogenesis into the vitreous, termed intravitreal neovascularization (IVNV). Although agents that interfere with the bioactivity of vascular endothelial growth factor (VEGF) are now used to treat IVNV, concerns exist regarding the identification of optimal doses of anti-VEGF for individual infants and the effect of broad VEGF inhibition on physiologic angiogenesis in external organs or in the retina of a preterm infant. Therefore, it is important to understand VEGF signaling in both physiologic and pathologic angiogenesis in the retina. In this manuscript, we review the role of receptors that interact with VEGF in oxygen-induced retinopathy (OIR) models that represent features of ROP pathology. Specifically, we discuss our work regarding the regulation of VEGFR2 signaling in retinal endothelial cells to not only reduce severe ROP but also facilitate physiologic retinal vascular and neuronal development.


2010 ◽  
Vol 30 (9) ◽  
pp. 2120-2134 ◽  
Author(s):  
Peter Noy ◽  
Hannah Williams ◽  
Anyaporn Sawasdichai ◽  
Kevin Gaston ◽  
Padma-Sheela Jayaraman

ABSTRACT The proline-rich homeodomain protein (PRH) plays multiple roles in the control of gene expression during embryonic development and in the adult. Vascular endothelial growth factor (VEGF) is a mitogen that stimulates cell proliferation and survival via cell surface receptors including VEGFR-1 and VEGFR-2. VEGF signaling is of critical importance in angiogenesis and hematopoiesis and is elevated in many tumors. Here we show that PRH binds directly to the promoter regions of the Vegf, Vegfr-1, and Vegfr-2 genes and that in each case PRH represses transcription. We demonstrate that overexpression or knockdown of PRH directly impinges on the survival of both leukemic and tumor cells and that the modulation of VEGF and VEGF receptor signaling by PRH mediates these effects. Our findings demonstrate that PRH is a key regulator of the VEGF signaling pathway and describe a mechanism whereby PRH plays an important role in tumorigenesis and leukemogenesis.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Xiaofeng Hu ◽  
Hongru Xing ◽  
Xiaofeng Wang ◽  
Lei Du ◽  
Yihong Huang ◽  
...  

LncRNA SNHG1 (SNHG1) has been widely studied as the causative factor of angiogenesis and proliferative agent in gastric, lung, cervical, and hepatocellular carcinomas. However, its significance of angiogenesis and progression of corneal neovascularization (CRNV) is least understood. This study focuses on the molecular mechanisms followed by SNHG1 to establish CRNV and its angiogenesis. Bioinformatics analysis to identify potential miRNA targets of SNHG1 and vascular endothelial growth factor A (VEGF-A) was conducted using StarBase and was subsequently confirmed by the luciferase reporter assay. Relative quantitative expression of SNHG1 in human umbilical vein endothelial cells (HUVECs) was detected through qRT-PCR and western blot analysis. Cell proliferation was detected through CCK-8 assay, whereas migratory abilities of the cells were determined with transwell assay. A capillary-like tube formation assay was performed to detect the tube formation ability of the cells. Following this, relative expression of miR-195-5p and VEGF-A was determined through qRT-PCR and western blot analysis. Results from the experiments manifested upregulated levels of SNHG1 and VEGF-A in HUVECs and CRNV tissues as compared with the control group, whereas downregulated levels of miR-195-5p were measured in the CRNV tissues and HUVECs, suggesting the negative correlation between lncRNA and miRNA. Overexpressed vascular endothelial growth factor promoted cell proliferation and tube formation; however, its silencing leads to inhibition in angiogenesis and proliferation. Potential binding sites of SNHG1 showed miR-195-5p as its direct target and SNHG1 as a sponge for this miRNA. Knockdown and downregulated levels of SNHG1 showed a notable decrease and inhibition in angiogenesis and migration of CRNV cells. The study showed that SNHG1 inhibition significantly reduced cell proliferation, migration, and tube formation in HUVECs transfect with lncRNA SNHG1. Mechanistic insights into the SNHG1 showed that SNHG1 acts as a sponge for miR-195-5p and upregulates the levels of VEGF-A.


Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 253-260 ◽  
Author(s):  
Noriyuki Takahashi ◽  
Masanori T. Itoh ◽  
Bunpei Ishizuka

The intermediate filament protein nestin was originally found to be expressed in neuronal progenitor cells, but recent studies have shown that other cell types, including endocrine and vascular endothelial cells, express nestin. In the present study, we examined the expression and localization of nestin in the ovaries of developing, peripubertal, and adult rats. RT-PCR and Western blot analyses revealed that nestin mRNA and proteins were expressed in adult rat ovaries. Immunohistochemical analyses using adult rat ovaries showed that nestin was mainly localized to capillary endothelial cells of theca interna in follicles with more than two layers of granulosa cells and that its expression increased with follicle growth. Ontogenetically, ovarian nestin expression started at the peripubertal period when the first gonadotropin surge occurs. To test the possibility that gonadotropins induce nestin expression, prepubertal (postnatal d 21) rats were sc injected with equine chorionic gonadotropin (eCG) and/or human chorionic gonadotropin (hCG). A single injection of hCG, but not eCG, was sufficient to induce nestin expression in follicles, mainly in capillary endothelial cells of theca interna. Furthermore, pretreatment with an inhibitor of vascular endothelial growth factor receptor prevented the induction of the nestin expression by hCG. These findings demonstrate that the endogenous LH surge induces nestin expression in capillary endothelial cells of theca interna via the vascular endothelial growth factor signaling pathway. Nestin may be involved in angiogenesis in growing follicles, which is followed by follicle maturation and subsequent ovulation.


2021 ◽  
Vol 16 (1) ◽  
pp. 266-276
Author(s):  
Zhenfen Wang ◽  
Qing Liu ◽  
Ping Huang ◽  
Guohao Cai

Abstract Gastric cancer (GC) is ranked the fourth leading cause of cancer-related death, with an over 75% mortality rate worldwide. In recent years, miR-299-3p has been identified as a biomarker in multiple cancers, such as acute promyelocytic leukemia, thyroid cancer, and lung cancer. However, the regulatory mechanism of miR-299-3p in GC cell progression is still largely unclear. Cell viability and apoptosis tests were performed by CCK8 and flow cytometry assay, respectively. Transwell assay was recruited to examine cell invasion ability. The interaction between miR-299-3p and PAX3 was determined by the luciferase reporter system. PAX3 protein level was evaluated by western blot assay. The expression of miR-299-3p was downregulated in GC tissues and cell lines (MKN-45, AGS, and MGC-803) compared with the normal tissues and cells. Besides, overexpression of miR-299-3p significantly suppressed proliferation and invasion and promoted apoptosis in GC. Next, we clarified that PAX3 expression was regulated by miR-299-3p using a luciferase reporter system, qRT-PCR, and western blot assay. Additionally, downregulation of PAX3 repressed GC cell progression. The rescue experiments indicated that restoration of PAX3 inversed miR-299-3p-mediated inhibition on cell proliferation and invasion. miR-299-3p suppresses cell proliferation and invasion as well as induces apoptosis by regulating PAX3 expression in GC, representing desirable biomarkers for GC diagnosis and therapy.


Sign in / Sign up

Export Citation Format

Share Document