scholarly journals Polymorphism in the progesterone receptor promoter gene in endometrial cancer alters its expression

2020 ◽  
Author(s):  
Zhengwu Xiao ◽  
Huahua Xiang ◽  
Jing Zhou ◽  
Chen Zhou ◽  
Zifen Guo

Abstract The purpose of this study was to investigate the effect of progesterone receptor (PGR) promoter +331G/A polymorphism on the mRNA and protein expression of its two isoforms, PRA and PRB, in healthy control women and women with endometrial cancer. To evaluate the relative occurrence of +331G/A polymorphism, the PGR gene promoter in the whole blood of 66 healthy volunteers and 62 endometrial cancer patients was genotyped. The results demonstrate that the frequency of GG and the overall frequency of the G allele were >90% in both populations. The GA+AA genotypes were more common in the healthy control group than in the endometrial cancer group, though the differences were not statistically significant. RT-PCR and Western blot analysis results showed that the mRNA and protein levels of both PRB and PRA were significantly lower in endometrium from cancer patients than in normal endometrium tissue. Furthermore, among individuals with endometrial cancer, those with the +331 G/A polymorphism expressed higher mRNA levels of the PRA isoform and higher protein levels of the PRB isoform. Therefore, our findings suggest that patients with endometrial cancer express less PGR and that the mRNA and protein expression of PRA and PRB may be altered due to 331G/A PGR gene polymorphism.

2017 ◽  
Vol 131 (22) ◽  
pp. 2707-2719 ◽  
Author(s):  
Carlos-Ernesto Fernandez-García ◽  
Carlos Tarin ◽  
Raquel Roldan-Montero ◽  
Diego Martinez-Lopez ◽  
Monica Torres-Fonseca ◽  
...  

Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients (n=225) compared with the control group (n=100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Wen-cong Li ◽  
Su-xian Zhao ◽  
Wei-guang Ren ◽  
Hui-juan Du ◽  
Yu-guo Zhang ◽  
...  

The liver is the only visceral organ that exhibits a remarkable capability of regenerating in response to partial hepatectomy (PH) or chemical injury. Improving liver regeneration (LR) ability is the basis for the favourable treatment outcome of patients after PH, which can serve as a potential indicator for postoperative survival. The present study aimed to investigate the protective effects of Yiqi Huoxue recipe (YQHX) on LR after PH in rats and further elucidate its underlying mechanism. A two-thirds PH rat model was used in this study. Wistar rats were randomly divided into four groups: sham-operated, PH, YQHX + PH, and Fuzheng Huayu decoction (FZHY) + PH groups. All rats were sacrificed under anesthesia at 24 and 72 h after surgery. The rates of LR were calculated, and the expression levels of cyclin D1 and c-jun were determined by immunohistochemical staining. The protein levels of p-JNK1/2, JNK1/2, p-c-jun, c-jun, Bax, and Bcl-2 were detected by Western blotting, while the mRNA levels of JNK1, JNK2, c-jun, Bax, and Bcl-2 were examined by real-time polymerase chain reaction (RT-PCR). At the corresponding time points, YQHX and FZHY administration dramatically induced the protein levels of p-JNK1/2 compared to the PH group p<0.05, while FZHY + PH group showed prominently increase in p-JNK1/2 protein levels compared to the YQHX + PH group p<0.05. A similar trend was observed for the expression levels of p-c-jun. Compared to the PH group, YQHX and FZHY markedly reduced the mRNA and protein expression levels of Bax at 24 h after PH, while those in the FZHY + PH group decreased more obviously p<0.05. Besides, in comparison with the PH group, YQHX and FZHY administration predominantly upregulated the mRNA and protein expression levels of Bcl-2 at 24 and 72 h after PH p<0.05. In conclusion, YQHX improves LR in rats after PH by inhibiting hepatocyte apoptosis via the JNK signaling pathway.


2006 ◽  
Vol 291 (5) ◽  
pp. R1490-R1498 ◽  
Author(s):  
Arash Shahsavarani ◽  
Steve F. Perry

We indirectly tested the idea that the epithelial Ca2+ channel (ECaC) of the trout gill is regulated in an appropriate manner to adjust rates of Ca2+ uptake. This was accomplished by assessing the levels of gill ECaC mRNA and protein in fish exposed to treatments known to increase or decrease Ca2+ uptake capacity. Exposure of trout to soft water ([Ca2+] = 20–30 nmol/l) for 5 days (a treatment known to increase Ca2+ uptake capacity) caused a significant increase in ECaC mRNA levels and an increase in ECaC protein expression. The inducement of hypercalcemia by infusing fish with CaCl2 (a treatment known to reduce Ca2+ uptake) was associated with a significant decrease in ECaC mRNA levels, yet protein levels were unaltered. ECaC mRNA and protein expression were increased in fish treated with the hypercalcemic hormone cortisol. Finally, exposure of trout to 48 h of hypercapnia (∼7.5 mmHg, a treatment known to increase Ca2+ uptake capacity) elicited an ∼100-fold increase in the levels of ECaC mRNA and a significant increase in protein expression. Immunocytochemical analysis of the gills from hypercapnic fish suggested a marked increase in the apical expression of ECaC on pavement cells and a subpopulation of mitochondria-rich cells. The results of this study provide evidence that Ca2+ uptake rates are, in part, regulated by the numbers of apical membrane Ca2+ channels that, in turn, modulate the inward flux of Ca2+ into gill epithelial cells.


2018 ◽  
Vol 23 (3) ◽  
pp. 173-180 ◽  
Author(s):  
Junming Chen ◽  
Xiaowei Zhou ◽  
Tuanming Zou ◽  
Bochen  Wang ◽  
Youjun Yu ◽  
...  

Survival of cochlear sensory epithelial cells may be regulated by inhibitor of differentiation-1 (Id1) and the N-methyl-D-aspartic acid (NMDA) receptor. However, it is unclear whether Id1 and the NMDA receptor are involved in the radiation-mediated survival of rat cochlear sensory epithelial cells. Here, we show that the percentage of apoptotic cells increased, the percentage of cells in the S phase decreased, Id1 mRNA and protein expression decreased and the NMDA receptor subtype 2B (NR2B) mRNA and protein level increased in OC1 cells after radiation. Cells infected with the Id1 gene exhibited higher Id1 mRNA and protein levels and lower NR2B mRNA and protein levels than the control cells. In contrast, after transfection of the Id1 siRNA into OC1 cells, Id1 mRNA and protein expression decreased and NR2B mRNA and protein expression increased relative to that of the control group. Additionally, treatment with ifenprodil for 24 h before radiation reduced apoptosis and increased the percentage of cells in the S phase. Our results suggest that Id1 and NR2B might regulate the survival of OC1 cells following radiation.


2021 ◽  
Vol 11 (24) ◽  
pp. 11880
Author(s):  
Justyna Magiełda-Stola ◽  
Grażyna Kurzawińska ◽  
Marcin Ożarowski ◽  
Anna Bogacz ◽  
Hubert Wolski ◽  
...  

(1) Background: Considerable evidence indicates that the occurrence of preeclampsia (PE) is associated with a reduced vitamin D (VD) level. Several studies have found that VD deficiency is correlated with disturbed trophoblast invasion, reduced angiogenesis and increased vasoconstriction. Because the vitamin D receptor (VDR) and CYP27B1 and CYP2R1 hydrolases are strongly involved in VD metabolism, the goal of the present study was to evaluate their genes and proteins expression in the placentas from preeclamptic women. (2) Methods: Samples and clinical data were obtained from 100 Polish women (41 women with preeclampsia and 59 healthy pregnant controls). The whole PE group was divided into subgroups according to gestation week of pregnancy ending before and after 34 gestational weeks (early/late-onset preeclampsia (EOPE/LOPE)). However, finally, to reduce confounding by differences in gestational age, the EOPE group was excluded from the analysis of mRNA and protein placental expression, and we focus on the comparison between LOPE and control groups. The placental VDR, CYP27B1 and CYP2R1 mRNA expression was analyzed using RT-PCR, and placental protein levels were determined by ELISA assay. (3) Results. (3.1) Placental gene expression: Expression levels of both genes, CYP27B1 (1.17 vs. 1.05 in controls, p = 0.006) and CYP2R1 (2.01 vs. 1.89 in controls, p = 0.039), were significantly higher in preeclamptic placentas than in the control group. Interestingly, VDR expression was significantly lower in placentas from the PE group (1.15 vs. 1.20 in controls, p = 0.030). After dividing all preeclamptic women into subgroups only for the CYP27B1 gene, a significantly higher placental expression in the LOPE subgroup than the healthy controls was observed (padj = 0.038). (3.2) Placental protein expression: The results revealed that protein expression levels of CYP27B1 in the preeclamptic group were similar (5.32 vs. 5.23 in controls, p = 0.530). There was a significant difference in median VDR and CYP2R1 protein levels between studied groups (VDR: 2.56 vs. 3.32 in controls, p < 0.001; CYP2R1: 1.32 vs. 1.43 in controls, p = 0.019). After stratification of preeclamptic women into subgroups, a significant difference was observed only in the VDR protein level. The medians in the LOPE subgroups were significantly lower compared to the healthy control group. In the whole study group, the placental VDR protein level was inversely correlated with systolic and diastolic blood pressure (all p < 0.001), and positively correlated with gestational age (p < 0.001) and infant birth weight (p = 0.014). (4) Conclusions: Lower mRNA and protein expression of VDR in preeclamptic placentas, and also VDR protein expression, could play a pivotal role in preeclampsia development. Additionally, the higher mRNA expression of both CYP27B1 and CYP2R1 hydrolase genes in placentas from preeclamptic women could indicate the compensatory role of these enzymes in preeclampsia etiology. Our results also indicate that placental VDR protein level could be one of the factors modulating blood pressure in pregnant women, as well as influencing gestational age and infant birth weight. Considering the importance of these findings, future studies are warranted.


Author(s):  
Ida Marija Sola ◽  
Alan Serman ◽  
Valentina Karin-Kujundzic ◽  
Frane Paic ◽  
Anita Skrtic ◽  
...  

Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic mediators involved in canonical and non-canonical Wnt signaling that are important in embryonic development. The role of DVL proteins in the placental tissue remains mostly unknown. In the current study, we explored the role of Dishevelled proteins in naturally invasive tissue, trophoblast. Formalin-fixed paraffin-embedded samples of 15 term placentas from physiologic term pregnancies and 15 term placentas from pregnancies complicated with intrauterine growth restrictions (IUGR) were used for the study. Expression levels of mRNA for DVL1, DVL2, and DVL3 in placentas were analyzed by quantitative real-time PCR (qRT-PCR). DVL1, DVL2, and DVL3 protein expression were semi-quantitatively analyzed using immunohistochemistry. The expression of DVL2 and DVL3 proteins was significantly higher in trophoblasts in placental villi from IUGR pregnancies compared with the control group of term placentas. In contrast, DVL3 protein expression was significantly higher in endothelial cells in placental villi from IUGR pregnancies compared with normal term placentas. The observed differences at protein levels between normal and IUGR placentas were not confirmed at the mRNA levels of DVL genes. Our data indicate the active involvement of DVL proteins in IUGR-related placentas. No significant changes were observed in DVL mRNA levels between the two groups of placentas. Further studies are required to explore the clinical relevance of these observations.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Bin Zhang ◽  
Dong Li ◽  
Gexiu Liu ◽  
Wenfeng Tan ◽  
Jun Guo ◽  
...  

Objective. To investigate the effect of traditional Chinese antihypertensive compound Xinmaitong on blood pressure and vasoactive factors of vasoconstrictor endothelin-1 (ET-1) and vasodilator calcitonin gene related peptide (CGRP) in spontaneously hypertensive rats (SHRs) with early stage hypertension. Methods. Twenty male SHRs were randomly divided into two groups: 10 for hypertensive control group and 10 for hypertensive treatment group. In addition, 10 Wistar rats were used as the normal control group without any intervention. SHRs of hypertensive treatment group were orally treated with Xinmaitong, while the hypertensive control group was treated with the normal saline (NS) for a total of eight weeks. The blood pressure in SHRs was examined before and after the end of the eight-week study. After treatment, the rats were killed and the blood samples were collected to measure plasma levels of ET-1 and CGRP by ELISA method, respectively. Meanwhile, the aorta rings were isolated for measuring the mRNA expression of ET-1 and CGRP by PCR. Moreover, the protein levels of ET-1 and CGRP were studied by immunohistochemical. Results. Daily oral administration of Xinmaitong resulted in significant fall in the SHRs’ blood pressure, including systolic and diastolic blood pressures (SBP and DBP), mean blood pressure (MBP), and pulse pressure (PP). The plasma ET-1 levels were reduced and CGRP increased. In parallel, the mRNA and protein expression of ET-1 were decreased, whereas the mRNA and protein expression of CGRP were enhanced in SHRs treated with Xinmaitong. Conclusion. The present study demonstrated for the first time that Xinmaitong leads to the fall in blood pressure of SHRs and that this antihypertensive effect is, at least in part, due to improvement of arterial tone.


2014 ◽  
Vol 26 (7) ◽  
pp. 1007 ◽  
Author(s):  
Barbara Jana ◽  
Joanna Czarzasta ◽  
Jerzy Jaroszewski

Leukotrienes (LTs) are lipid mediators that play a significant role in the inflammatory process. Their production in inflamed uteri is not fully understood. The present experiment aimed to determine LTB4 and LTC4 amounts, 5-lipooxygenase (5-LO), LTA4 hydrolase (LTAH) and LTC4 synthase (LTCS) mRNA levels and protein expression in inflamed porcine uteri. On Day 3 of the oestrous cycle (Day 0 of the study), either Escherichia coli suspension or saline were infused into uterine horns. Collection of uterine tissues and washings took place eight or sixteen days later. In gilts suffering from endometritis increased LTB4 and LTC4 levels in the endometrium and washings and 5-LO mRNA levels in the myometrium on Days 8 and 16, 5-LO protein levels in the endometrium and myometrium on Day 8, LTAH mRNA and protein levels in the endometrium and myometrium on Days 8 and 16, respectively. Although LTCS mRNA and protein expression in the myometrium and LTCS protein expression in the endometrium were enhanced on Day 16 after Escherichia coli inoculation, LTCS mRNA levels decreased on Day 8 in both tissues. Our study shows the upregulation of LT production in inflamed porcine uteri, which suggests the importance of these factors to the process of uterine inflammation.


2019 ◽  
Vol 31 (4) ◽  
pp. 810 ◽  
Author(s):  
Onalenna Kereilwe ◽  
Hiroya Kadokawa

Anti-Müllerian hormone (AMH) is secreted from ovaries and stimulates gonadotrophin secretion from bovine gonadotroph cells. Other important hormones for endocrinological gonadotroph regulation (e.g. gonadotrophin-releasing hormone, inhibin and activin) have paracrine and autocrine roles. Therefore, in this study, AMH expression in bovine gonadotroph cells and the relationships between AMH expression in the bovine anterior pituitary (AP) and oestrous stage, age and breed were evaluated. AMH mRNA expression was detected in APs of postpubertal heifers (26 months old) by reverse transcription-polymerase chain reaction. Based on western blotting using an antibody to mature C-terminal AMH, AMH protein expression was detected in APs. Immunofluorescence microscopy utilising the same antibody indicated that AMH is expressed in gonadotrophs. The expression of AMH mRNA and protein in APs did not differ between oestrous phases (P&gt;0.1). We compared expression levels between old Holsteins (79.2±10.3 months old) and young (25.9±0.6 months old) and old Japanese Black females (89.7±20.3 months old). The APs of old Holsteins exhibited lower AMH mRNA levels (P&lt;0.05) but higher AMH protein levels than those of young Japanese Black females (P&lt;0.05). In conclusion, bovine gonadotrophs express AMH and this AMH expression may be breed-dependent.


Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ying Xie ◽  
Yuanyuan Ruan ◽  
Huimei Zou ◽  
Yixin Wang ◽  
Xin Wu ◽  
...  

<b><i>Objective:</i></b> The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. <b><i>Methods:</i></b> C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. <b><i>Results:</i></b> Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. <b><i>Conclusion:</i></b> YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.


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