scholarly journals Expression and Potential Role of MMP-9 in Intrauterine Adhesion

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Congqing Li ◽  
Wenyan Wang ◽  
Shiying Sun ◽  
Youjiang Xu ◽  
Ziang Fang ◽  
...  

Objective. Intrauterine adhesions affect menstruation and fertility, and endometrial fibrosis is the final manifestation of IUA. MMP-9 is closely related to fibrosis. The purpose of the study was to assess the role of MMP-9 in intrauterine adhesion (IUA) in rats and patients. Methods. 40 rats and 24 women were enrolled in this study. 40 rats were randomly divided into 3 groups: IUA group ( n = 20 ), sham group ( n = 10 ), and control group ( n = 10 ). Rat IUA models were established by intrauterine mechanical and chemical injured. In this study, 12 patients of intrauterine adhesions were detected and underwent TCRA (transcervical resection of adhesion) surgery, and endometrial tissue specimens were obtained during operation. One month later, an office hysteroscopy procedure was performed, and endometrial tissue specimens were obtained during operation again (postoperative group). A group of 12 normal age-matched control individuals served as controls underwent hysteroscopy and endometrial sampling. We used immunohistochemistry to detect MMP-9 expressions in rats and human endometrial tissues and to detect MMP-9 protein levels by Western blotting. In addition, we detected mRNA expression levels with qRT-PCR. Results. The expression of MMP-9 in the IUA rats was reduced compared with that in the sham group and Ctrl group ( P < 0.05 ), and the expression of MMP-9 was also reduced in the IUA patients compared with that in the Ctrl group ( P < 0.05 ). The mRNA levels of MMP-9 in the endometrium reflected similar results ( P < 0.05 ). The MMP-9 clearly increased even in the endometrium after TCRA surgery ( P < 0.05 ). Conclusion. Our study suggests that MMP-9 may play an important role in IUA. In the future, more in-depth research should be conducted on MMP-9.


2020 ◽  
Author(s):  
Congqing Li ◽  
Lin Cong ◽  
Youjiang Xu ◽  
Wenyan Wang

Abstract Background: Intrauterine adhesions will affect the amount of menstrual and fertility, endometrial fibrosis is the last manifestation of the IUA. MMP-9 is closely related to fibrosis. The purpose of the study was to assess the role of MMP-9 in intrauterine adhesion (IUA) rats and patients.Methods:40 female rats and 24 patients were enrolled in this study. We used immunohistochemistry to detect the MMP-9 expression in rats and human endometrial tissues, as well as detected their protein levels with western blot. In addition, we detected their mRNA expression levels with qRT-PCR.Results: The expression of MMP-9 in the IUA rats was reduced compared with the Sham group and Ctrl group (P< 0.05), and the expression of MMP-9 was also reduced in the IUA patients compared with the Ctrl group (P< 0.05). The mRNA levels of MMP-9 in endometrium were presenting similar results (P< 0.05). Conclusions: Our study suggests that MMP-9 may play an important role in fibrosis of the IUA. It may provide a new reference for the treatment of IUA in the future.



2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chu Qin ◽  
Xiao-yan Sai ◽  
Xiu-fen Qian ◽  
Yan Wu ◽  
Li-fei Zou ◽  
...  

Background. cIAP2 is involved in necroptosis as a key upstream regulation factor. We aimed to investigate the role of cIAP2 in ARDS/ALI induced by H7N9 virus through regulating the RIPK1/3 necroptosis pathway.Methods. Lung tissues of 11 patients who died from ARDS-complicated H7N9 infection between 2013 and 2016 were obtained as the H7N9-ARDS group. Lung tissues near benign lung nodules were acquired as the control group. Histological changes were evaluated by H&E staining. Protein levels of cIAP2, RIPK1, RIPK3, p-RIPK3, MLKL, and p-MLKL in the lung tissues were detected by Western Blot. The mRNA levels of cIAP2, RIPK1, and RIPK3 were detected by real-time PCR.Results. H7N9 virus infection had a high mortality, with ARDS being the leading cause of death. The protein level of cIAP2 in the experimental group was lower than that in the control group (P<0.05). However, the experimental group showed higher RIPK1, RIPK3, and p-RIPK3 protein levels than the control group (P<0.05), as well as the expression level of MLKL and p-MLKL protein, which is a key downstream protein in necroptosis (P<0.05).Conclusion. In tissues from patients with fatal H7N9, downregulation of cIAP2 and induction of necroptosis was observed. We could speculate that necroptosis of the pulmonary epithelium is associated with severe H7N9 infection leading to ARDS. Thus, necroptosis inhibition may be a novel therapy for H7N9 influenza virus.



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.



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.



2021 ◽  
Vol 22 (3) ◽  
pp. 1478
Author(s):  
Jiayin Lu ◽  
Yaoxing Chen ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.



2012 ◽  
Vol 120 (02) ◽  
pp. 84-88 ◽  
Author(s):  
S. Chen ◽  
X. Zhuang ◽  
Y. Liu ◽  
A. Sun ◽  
C. Chen

AbstractLipin1, a lately indentified adipokine, may link obesity with insulin resistance and diabetes. The present study aimed to investigate the changes and significance of lipin1 expression and lipin1-AMPK signaling in diet-induced hepatic insulin resistance.24 4-week-old Male Wistar rats were randomly divided into 2 groups: (1) control group (CO), (2) high-fat diet group (HF). Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique. The mRNA levels of α1 and α2 subunit of AMPKα as well as Lipin1 were measured using Real-time RT-PCR. The activities of AMPKα and Akt were evaluated by detection of p-AMPKα (Thr-172) and p-Akt (ser473) by Western blot.After treatment of 4 months, HF group showed significantly increased levels of body weight, fasting plasma glucose and insulin levels; Plasma and liver total cholesterol (TC), triglycerides (TG) levels were also markedly elevated; Lipin1 expression at both mRNA and protein levels were significantly deceased. Compared with CO group, the mRNA and protein levels of AMPKα1 and AMPKα2 were not changed, whereas the p-AMPK (Thr-172) and p-AKT (ser473) levels in liver were significantly decreased in HF group.These findings indicated that the decrease in lipin1 expression and AMPKα activation may contribute to hepatic insulin resistance in diet-induced obese rats.



2020 ◽  
Author(s):  
Jing Huang ◽  
Ming Ding ◽  
Ying Wu ◽  
Shuhua Han ◽  
Yan Xie ◽  
...  

Abstract Background Radioactive seed is a method for treating drug-resistant, late-stage non-small cell lung cancer (NSCLC), but has undesirable side effects. Gambogic acid (GA), an ingredient of traditional Chinese medicine, exerts broad-spectrum antitumour activities via several pathways. This study aimed to elucidate the mechanism involved in the combined effect of low-dose GA and NaI131 to sensitize the antitumour activity of NaI131 in drug-resistant NSCLC cells. Methods Human NSCLC cell line A549 and drug-resistant cell lines A549/DDP and A549/Taxol were treated with NaI131, low-dose GA or a combination of both; control group of each cell line was treated with phosphate-buffered saline. Following treatment, cell proliferation, apoptosis, cell cycle, and levels of expression of apoptosis-related proteins namely CDK1, Cyclin B, mtp53, HSP90, and Bax, Bcl-2 respectively, and P-glycoprotein 1 (P-gp) known to confer resistance to chemotherapy, were detected using western blotting and immunofluorescence. mRNA levels of mtp53 and HSP90 were measured using qRT-PCR. Results Compared to the control group, A549, A549/DDP, and A549/Taxol cells treated with NaI131, GA or combination of drugs exhibited G2/M arrest, increased percentage of total apoptotic cells, significantly reduced protein levels of CDK1, Cyclin B, mtp53, HSP90, Bcl-2 and P-gp, increased protein levels of Bax and decreased mRNA levels of mtp53 and HSP90. The changes in the combination group were significantly different from the other groups. Conclusion In NSCLC cell lines, low-dose GA could enhance the effect of NaI131 on G2/M arrest, promote cell apoptosis, reduce drug-resistance and hence could be explored as a potential radionuclide sensitizer.



Author(s):  
Porfyrios Korompelis ◽  
Christina Piperi ◽  
Christos Adamopoulos ◽  
Georgia Dalagiorgou ◽  
Penelope Korkolopoulou ◽  
...  

AbstractLeiomyomas growth involves cellular hypertrophy, modulation of mitotic activity and upregulation of extracellular matrix (ECM). Vascular factors and matrix metalloproteinases (MMPs) play a coordinated role during neoplasia and tissue remodeling. The present study investigates the role of angiogenic factor vascular endothelial growth factor (VEGF)-A with the activity of main gelatinases, MMP-2/MMP-9 and their tissue inhibitor TIMP-1 in patients with leiomyomas.Peripheral blood of 46 women with uterine leiomyomas was obtained prior hysterectomy to assess VEGF-A, MMP-2, -9, TIMP-1 levels by enzyme-linked immunosorbent assay compared to 39 healthy controls. Protein expression levels of VEGF-A, MMP-2 and MMP-9 were evaluated by western immunoblotting and immunohistochemistry in leiomyomas tissue specimens after hysterectomy. Furthermore, the activity of gelatinases in leiomyoma tissue extracts and control myometrium was evaluated by semi-quantitative zymography.Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patients compared to controls (p<0.001, p=0.004, p=0.003, respectively). A positive correlation was found between VEGF-A and MMP-2 (p=0.021) as well as MMP-9 (p=0.001) peripheral levels in the patient’s group. Furthermore, increased VEGF-A protein levels were detected in leiomyoma tissue compared to control myometrium, followed by increased localization of both VEGF-A and MMP-2 in the ECM embedding bundles of smooth muscle cells of leiomyomas. The activity of MMP-2 was significantly higher in leiomyomas than normal myometrium in all investigated tissues.This study demonstrates a possible coordinated role of VEGF-A and MMP-2 during uterine leiomyomas growth and angiogenesis with potential prognostic significance.



Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Akira Nishiyama ◽  
Juan Wang ◽  
Shinichi Yachida ◽  
Genevieve Nguyen ◽  
Takuo Hirose ◽  
...  

(Pro)renin receptor ((P)RR) is a component of the Wnt receptor complex (Science, 2010). We have recently demonstrated that (P)RR plays an important role in the tumorigenesis of pancreatic ductal adenocarcinoma via the activation of Wnt/β-catenin signaling pathway (Shibayama et al. Sci Rep. 2015). Since the patients with colon cancer often show aberrantly activated Wnt/β-catenin-dependent signaling pathway by the mutations of its components, we investigated the possible role of (P)RR and Wnt/β-catenin signaling pathway in carcinogenesis of colon cancer. Real-time PCR was used for measuring mRNA levels of (P)RR. Protein levels of (P)RR was determined by Western blotting and immunohistochemistry. Activated β-catenin levels were determined by Western blotting. Cell proliferative ability was evaluated by counting the cell number in cultured colon cancer cell lines, HCT116 and DLD-1 cells. As compared to normal colon tissues (n=6), mRNA and protein levels of (P)RR were increased by 2.6- and 2.2-fold, respectively, in colon cancer tissues (n=9), which were associated with increased activated β-catenin levels (by 2.8-fold, P<0.05). However, plasma soluble (P)RR levels were not changed in patients with colon cancer (n=9). (P)RR and activated β-catenin levels were also increased in HCT116 (by 2.2- and 2.7-fold, n=5, respectively) and DLD-1 cells (by 1.9- and 2.8-fold, n=5, respectively). In these cells, inhibiting (P)RR with an siRNA attenuated the activity of β-catenin and reduced the proliferative abilities (n=5, P<0.05, respectively). These data suggest that (P)RR contributes to the tumorigenesis of colon cancer through the activation of Wnt/β-catenin signaling pathway.



Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 104 ◽  
Author(s):  
Faiz Muhammad Khand ◽  
Da-Wei Yao ◽  
Pan Hao ◽  
Xin-Qi Wu ◽  
Asghar Ali Kamboh ◽  
...  

Early diagnosis of mammary gland tumors is a challenging task in animals, especially in unspayed dogs. Hence, this study investigated the role of microsatellite instability (MSI), MMR gene mRNA transcript levels and SNPs of MMR genes in canine mammary gland tumors (CMT). A total of 77 microsatellite (MS) markers in 23 primary CMT were selected from four breeds of dogs. The results revealed that 11 out of 77 MS markers were unstable and showed MSI in all the tumors (at least at one locus), while the other markers were stable. Compared to the other markers, the ABC9TETRA, MEPIA, 9A5, SCNA11 and FJL25 markers showed higher frequencies of instability. All CMT demonstrated MSI, with eight tumors presenting MSI-H. The RT-qPCR results revealed significant upregulation of the mRNA levels of cMSH3, cMLH1, and cPMSI, but downregulation of cMSH2 compared to the levels in the control group. Moreover, single nucleotide polymorphisms (SNPs) were observed in the cMSH2 gene in four exons, i.e., 2, 6, 15, and 16. In conclusion, MSI, overexpression of MMR genes and SNPs in the MMR gene are associated with CMT and could be served as diagnostic biomarkers for CMT in the future.



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