Browsing by Subject "β-catenin"
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- PublicationOpen AccessAberrant levels of Wnt/β-catenin pathway components in a rat model of endometriosis(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Medina de Mattos, Rômulo; Rodrigues Pereira, Paula; Gouvêa de Oliveira Barros, Eliane; Henriques da Silva, Julianna; Yelimar Palmero, Celia; Meireles da Costa, Nathália; Ribeiro Pinto, Luis Felipe; Rodrigues Pereira Gimba, Etel; Hecht, Fábio; Bueno Ferreira, Luciana; Escorsim Machado, Daniel; Leite de Oliveira, Felipe; Eurico Nasciutti, LuizEndometriosis is a benign gynecological disease affecting approximately 10-15% of women of reproductive age and 25-50% of all infertile women. It is characterized by the presence of glands and/or endometrial stroma outside the uterine cavity. Angiogenesis is a crucial process for the development and maintenance of endometriotic lesions. The Wnt/βcatenin pathway is a major promoter of angiogenesis in both physiological and pathological conditions. In the present study, we evaluated the expression of molecules related to the Wnt/β-catenin pathway in a rat model of peritoneal endometriosis. mRNA analyses showed significantly increased expression of Wnt4 and Wnt7b and decreased expression of Gsk3beta and E-cadherin in endometriotic lesions. However, there were no differences in β-catenin and Fzd2 mRNA expression. In addition, we observed a significant increase of nuclear β-catenin in endometriotic lesions, a hallmark of Wnt/ β -catenin pathway activation. Stromal β-catenin staining was found in 45.4% of endometrial tissues and 77.8% of endometriotic lesions. β-catenin nuclear localization was found in 18.2% of the endometrial tissues and 33.3% of endometriotic lesions. Finally, the expression of galectin-3, a regulator of this pathway, was increased in endometriosis. In summary, this pattern of Wnt/βcatenin components expression suggests an increased activity of this pathway in endometriosis.
- PublicationOpen AccessFlutamide alters β-catenin expression and distribution, and its interactions with E-cadherin in the porcine corpus luteum of mid- and late pregnancy(Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Grzesiak, Malgorzata; Mitan, Agata; Janik, Marcelina E.; Knapczyk-Stwora, Katarzyna; Slomczynska, MariaThis study examined whether flutamideinduced androgen deficiency during mid- and late pregnancy in pigs affected luteal expression of adherens junction protein, β-catenin, and its interactions with Ecadherin. Flutamide (50 mg/kg body weight) was administered into pregnant gilts between days 43-49 (GD50F), 83-89 (GD90F) or 101-107 (GD108F) of gestation. Corpora lutea (CLs) were obtained on day 50, 90 or 108 of pregnancy (n=8-11 per each group). Total β-catenin and E-cadherin expression was examined at mRNA (real-time PCR) and protein (Western blot) level. Moreover, subcellular β-catenin fractions were extracted and immunoblotted. Immunohistochemistry was used for β-catenin localization. To determine whether flutamide disturbs β-catenin/E-cadherin mutual interactions, coimmunoprecipitation using anti-β-catenin antibody was performed. Furthermore, phosphorylation of Ecadherin was assessed. Flutamide exposure led to decreased β-catenin mRNA expression in all examined groups (p<0.001 or p<0.01), but protein level was lower only in the GD90F and GD108F groups (p<0.05). Ecadherin mRNA (p<0.05 or p<0.01) and protein (p<0.05) levels were up-regulated in all flutamidetreated groups when compared to controls. β-catenin was predominantly found in membranes of luteal cells with no significant changes after antiandrogen treatment. βcatenin/E-cadherin complexes were more abundant in the GD90F (p<0.05) and GD108F (p<0.01) groups than in controls due to enhanced E-cadherin phosphorylation at serine 838/840 in those animals (p<0.05). Overall, although androgen deficiency affected β-catenin expression in the CL of pregnancy in pigs, a compensatory mechanism by enhanced interactions with E-cadherin is possible. Thus, androgen signaling via androgen receptors appears to be crucial in the regulation of luteal cells cross-talk.
- PublicationOpen AccessIncreased annexin A2 and decreased β-catenin in adenomyosis contribute to adenomyosis-associated dysmenorrhea(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Liu, Li Xue; Wu, Yin Ga; Zheng, JianObjective. To investigate the expression of annexin A2 (ANXA2) and β-catenin in eutopic and ectopic endometrium, and their relationships with adenomyosis-associated dysmenorrhea. Methods. From December 2013 to June 2014, ectopic endometrium (n=30) and eutopic endometrium (n=30) of adenomyosis were collected as experimental group, and endometrium (n=30) of uterine myoma as control group from the department of gynecology and obstetrics, the affiliated hospital of Inner Mongolia medical university. The expression of ANXA2 and βcatenin was detected by immunohistochemical S-P method, followed by the Pearson correlations for the correlation analysis of ANXA2 and β-catenin with adenomyosis-associated dysmenorrhea. Meanwhile, the levels of preoperative serum ANXA2 of patients with adenomyosis (n=42) and uterine myoma (n=42) were also measured by enzyme-linked immunosorbent assay (ELISA). Results. Immunohistochemistry and ELISA identified a higher expression of ANXA2 in eutopic and ectopic endometrium of adenomysis tissues, whereas βcatenin protein was down-regulated. Furthermore, there was a significant positive correlation between ANXA2 expression and dysmenorrhea degree, while there was a negative linear correlation between β-catenin expression and dysmenorrhea degree in ectopic endometrium. Conclusion. These results suggested that increased ANXA2 and less expressed β-catenin were correlated to adenomyosis-associated dysmenorrhea. It may provide a new idea of diagnosis and treatment to adenomyosisassociated dysmenorrhea.
- PublicationOpen AccessPrognostic significance of E-cadherin, β-catenin and cyclin D1 in oral squamous cell carcinoma: a tissue microarray study(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Al-Rawi, Natheer; Al Ani, Muwaffaq; Quadri, Asif; Hamdoon, Zaid; Awwad, Aktham; Al Kawas, Sausan; Al Nuaim, AhmedObjective. To study the prognostic significance of E-cadherin, β-catenin, and cyclin D1 expression in oral squamous cell carcinoma. Subjects and Methods. The study included 65 subjects with histologically confirmed squamous cell carcinoma. TMA blocks were prepared for immunohistochemical quantification of the expression of the three markers using IHC profiler and Immune ratio plugin of Image J. Results. E-cadherin expression was significantly correlated with histological grades and the metastasis status (p<0.05), whereas β-catenin expression was significantly correlated with smoking and tumor recurrence (P<0.05). Cyclin D1 expression was significantly correlated with depth of invasion and tumor recurrence. (p<0.05). Advanced tumor stage and depth of tumor invasion increases the risk of recurrence or death by 2.5 times (OR=2.53 and 0.84 respectively). Conclusion. High expression of β-catenin and cyclin D1 are significantly correlated with tumor recurrence and old age. Depth of invasion, low histological grade and old age were a significant predictor for the risk of having tumor recurrence and cancer related death.
- ItemOpen AccessPU.1 aggravates hepatic sinusoidal obstruction syndrome by upregulating PTBP1 and activating the Wnt/β-catenin pathway(2026) Yang, Li; Ju, Honglin; Chen, Zhiyuan; Cheng, Siqi; Liu, Ya; Wang, Xiangyang; Biología Celular e HistologíaObjective. Hepatic sinusoidal obstruction syndrome (HSOS) is a disease characterized by damage to hepatic sinusoidal endothelial cells (HSECs). This research investigates the role and regulatory pathway of PU box-binding protein (PU.1) in the progression of HSOS. Methods. We established an in vivo HSOS model through peritoneal administration of monocrotaline (MCT). Primary murine HSECs were isolated and treated with various concentrations of MCT to establish an in vitro HSOS model. PU.1 knockdown was achieved using lentiviral shRNA constructs, and its impact on oxidative stress, PTBP1 expression, β-catenin mRNA stability, and Wnt/β-catenin signaling was evaluated through kits, RT-qPCR, and western blot. Dual-luciferase and chromatin immunoprecipitation assays were conducted to assess the interaction between PU.1 and the PTBP1 promoter. The molecular association between PTBP1 and β-catenin mRNA was confirmed through RNA pull-down and RIP assays. Results. PU.1 was upregulated in MCT-induced HSOS, contributing to elevated oxidative stress and activation of the Wnt/β-catenin pathway. PU.1 directly enhanced PTBP1 transcription, which stabilized β-catenin mRNA and sustained Wnt/β-catenin signaling. PU.1 knockdown alleviated oxidative stress, reduced liver damage, and disrupted the PTBP1-β-catenin interaction, leading to Wnt/β-catenin activity inhibition. Overexpression of PTBP1 reversed the protective effects of PU.1 knockdown, reinstating oxidative stress and reactivating Wnt/β-catenin signaling. Conclusion. PU.1 facilitated HSOS pathogenesis by promoting the transcriptional activity of PTBP1 and activating the Wnt/β-catenin pathway. Targeting PU.1 can serve as a promising therapeutic strategy for reducing oxidative stress and liver damage in HSOS.
- PublicationOpen AccessWnt signaling in kidney tubulointerstitium during disease(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Maarouf, Omar H.; Ikeda, Yoichiro; Humphreys, Benjamin D.The evolutionary conserved Wnt signaling transduction pathway plays essential roles in a wide array of biologic processes including embryonic development, branching morphogenesis, proliferation and carcinogenesis. Over the past ten years it has become increasingly clear that Wnt signaling also regulates the response of adult organs to disease processes, including kidney disease. This review will focus on the growing literature implicating important roles for Wnt signaling during disease in two separate kidney compartments: the tubular epithelium and the interstitium.
- PublicationOpen AccessWNT Signaling in Tumors: The Way to Evade Drugs and Immunity(Frontiers, 2019-12-20) Martin-Orozco, Elena; Sánchez-Fernández, Ana; Ortíz-Parra, Irene; Ayala San Nicolás, María; Martín-Orozco Santiago, María Elena; Bioquímica y Biología Molecular B e InmunologíaWNT/β-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer stem cell (CSC) subset present in the tumor bulk. Related with this, WNT signaling has been associated with the maintenance, expansion, and epithelial-mesenchymal transition of stem cells, and furthermore with two distinctive features of this tumor population: therapeutic resistance (MDR, multidrug resistance) and immune escape. These mechanisms are developed and maintained by WNT activation through the transcriptional control of the genes involved in such processes. This review focuses on the description of the best known WNT pathways and the molecules involved in them. Special attention is given to the WNT cascade proteins deregulated in tumors, which have a decisive role in tumor survival. Some of these proteins function as extrusion pumps that, in the course of chemotherapy, expel the drugs from the cells; others help the tumoral cells hide from the immune effector mechanisms. Among the WNT targets involved in drug resistance, the drug extrusion pump MDR-1 (P-GP, ABCB1) and the cell adhesion molecules from the CD44 family are highlighted. The chemokine CCL4 and the immune checkpoint proteins CD47 and PD-L1 are included in the list of WNT target molecules with a role in immunity escape. This pathway should be a main target in cancer therapy as WNT signaling activation is essential for tumor progression and survival, even in the presence of the anti-tumoral immune response and/or antineoplastic drugs. The appropriate design and combination of anti-tumoral strategies, based on the modulation of WNT mediators and/or protein targets, could negatively affect the growth of tumoral cells, improving the efficacy of these types of therapies.