Bone Marrow Mesenchymal Stem Cells (BMSCs) Enhance Endometrial Stromal Cell Migration and Epithelial-Mesenchymal Transition in Adenomyosis Through Upregulation of Neuropilin 1

2022 ◽  
Vol 12 (2) ◽  
pp. 352-357
Author(s):  
Xiaofang Kang ◽  
Hongcheng Zhu
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Stress Factors ◽  
Drug Candidate ◽  
Therapeutic Drug ◽  
Human Escs ◽  
Endometrial Stromal Cells ◽  
Estrogen Regulation ◽  
Mesenchymal Transition ◽  
Neuropilin 1 ◽  
Junction Protein

Hormone support (estrogen and progesterone) is a key factor in decidualization and embryo implantation. Elevated levels of estrogen lead to luteal phase defects through Neuropilin 1, a membranecytoskeleton junction protein. This study aimed to explore the effect of BMSCs on endometrial stromal cells (ESCs) in adenomyosis. ESCs obtained from patients with adenomyosis were cocultured with BMSCs in the absence of presence of Neuropilin 1 inhibitor followed by analysis of expression of decidualization-related genes by RT-qPCR and western blot, cell viability by MTT assay, cell invasion and migration by Transwell assay, oxidative stress factors by ROS kit. Treatment with Neuropilin 1 inhibitor significantly decreased ESC proliferation and invasion, blocked epithelialmesenchymal transition (EMT) process, and restrained decidualization with a downregulation of decidualization-related genes. Furthermore, inhibition of Neuropilin 1 exerted effects through estrogen regulation. However, co-culture with BMSCs restored ESC activity by promoting Neuropilin expression and enhanced intrauterine ESC decidualization. In conclusion, Neuropilin 1 inhibitor restrains decidualization through estrogen regulation which can be abrogated by estrogen receptor antagonists. BMSCs restore the damaged ESC decidualization through increasing Neuropilin 1 expression, which provides new insights into the adverse effect of Neuropilin 1 on human ESCs, suggesting that BMSC is a potential therapeutic drug candidate for adenomyosis.

scholarly journals Circulating miRNAs Related to Epithelial–Mesenchymal Transitions (EMT) as the New Molecular Markers in Endometriosis

2021 ◽  
Vol 43 (2) ◽  
pp. 900-916
Author(s):  
Anna Zubrzycka ◽  
Monika Migdalska-Sęk ◽  
Sławomir Jędrzejczyk ◽  
Ewa Brzeziańska-Lasota
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Symptoms ◽  
Diagnostic Tools ◽  
Endometrial Stromal Cells ◽  
Disease Etiology ◽  
Diagnostic Biomarkers ◽  
Mesenchymal Transition ◽  
Non Invasive

Endometriosis is a chronic gynecological disease defined by the presence of endometrial-like tissue found outside the uterus, most commonly in the peritoneal cavity. Endometriosis lesions are heterogenous but usually contain endometrial stromal cells and epithelial glands, immune cell infiltrates and are vascularized and innervated by nerves. The complex etiopathogenesis and heterogenity of the clinical symptoms, as well as the lack of a specific non-invasive diagnostic biomarkers, underline the need for more advanced diagnostic tools. Unfortunately, the contribution of environmental, hormonal and immunological factors in the disease etiology is insufficient, and the contribution of genetic/epigenetic factors is still fragmentary. Therefore, there is a need for more focused study on the molecular mechanisms of endometriosis and non-invasive diagnostic monitoring systems. MicroRNAs (miRNAs) demonstrate high stability and tissue specificity and play a significant role in modulating a range of molecular pathways, and hence may be suitable diagnostic biomarkers for the origin and development of endometriosis. Of these, the most frequently studied are those related to endometriosis, including those involved in epithelial–mesenchymal transition (EMT), whose expression is altered in plasma or endometriotic lesion biopsies; however, the results are ambiguous. Specific miRNAs expressed in endometriosis may serve as diagnostics markers with prognostic value, and they have been proposed as molecular targets for treatment. The aim of this review is to present selected miRNAs associated with EMT known to have experimentally confirmed significance, and discuss their utility as biomarkers in endometriosis.

scholarly journals Role of Nuclear Claudin-4 in Renal Cell Carcinoma

2020 ◽  
Vol 21 (21) ◽  
pp. 8340
Author(s):  
Takuya Owari ◽  
Takamitsu Sasaki ◽  
Kiyomu Fujii ◽  
Rina Fujiwara-Tani ◽  
Shingo Kishi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tight Junction ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Nuclear Fraction ◽  
Mesenchymal Transition ◽  
Junction Protein

Claudin-4 (CLDN4) is a tight junction protein to maintain the cancer microenvironment. We recently reported the role of the CLDN4 not forming tight junction in the induction of epithelial-mesenchymal transition (EMT). Herein, we investigated the role of CLDN4 in renal cell carcinoma (RCC), focusing on CLDN4. CLDN4 expression in 202 RCCs was examined by immunostaining. CLDN4 phosphorylation and subcellular localization were examined using high metastatic human RCC SN12L1 and low metastatic SN12C cell lines. In 202 RCC cases, the CLDN4 expression decreased in the cell membrane and had no correlation with clinicopathological factors. However, CLDN4 was localized in the nucleus in 5 cases (2%), all of which were pT3. Contrastingly, only 6 of 198 nuclear CLDN4-negative cases were pT3. CLDN4 was found in the nuclear fraction of a highly metastatic human RCC cell line, SN12L1, but not in the low metastatic SN12C cells. In SN12L1 cells, phosphorylation of tyrosine and serine residues was observed in cytoplasmic CLDN4, but not in membranous CLDN4. In contrast, phosphorylation of serine residues was observed in nuclear CLDN4. In SN12L1 cells, CLDN4 tyrosine phosphorylation by EphA2/Ephrin A1 resulted in the release of CLDN4 from tight junction and cytoplasmic translocation. Furthermore, protein kinase C (PKC)-ε phosphorylated the CLDN4 serine residue, resulting in nuclear import. Contrarily, in SN12C cells that showed decreased expression of EphA2/Ephrin A1 and PKCε, the activation of EphA2/EphrinA1 and PKCε induced cytoplasmic and nuclear translocation of CLDN4, respectively. Furthermore, the nuclear translocation of CLDN4 promoted the nuclear translocation of Yes-associated protein (YAP) bound to CLDN4, which induced the EMT phenotype. These findings suggest that the release of CLDN4 by impaired tight junction might be a mechanism underlying the malignant properties of RCC. These findings suggest that the release of CLDN4 by impaired tight junction might be one of the mechanisms of malignant properties of RCC.

High-Expression of Neuropilin 1 Correlates to Estrogen-Induced Epithelial-Mesenchymal Transition of Endometrial Cells in Adenomyosis

2020 ◽  
Vol 27 (1) ◽  
pp. 395-403 ◽  
Author(s):  
Rong Hu ◽  
Guo-Qing Peng ◽  
De-Ying Ban ◽  
Chun Zhang ◽  
Xiao-Qiong Zhang ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
High Expression ◽  
Mesenchymal Transition ◽  
Endometrial Cells ◽  
Neuropilin 1

scholarly journals Neuropilin-1 Interacts with Fibronectin-1 to Promote Epithelial–Mesenchymal Transition Progress in Gastric Cancer

2020 ◽  
Vol Volume 13 ◽  
pp. 10677-10687
Author(s):  
Chao Wu ◽  
Meng-hua Zeng ◽  
Gang Liao ◽  
Kun Qian ◽  
Hui Li
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Neuropilin 1

scholarly journals MicroRNA-375: Potential cancer suppressor and therapeutic drug

2021 ◽  
Author(s):  
Jiahui Wei ◽  
Yiran Lu ◽  
Ruiqing Wang ◽  
Xiangzhu Xu ◽  
Qing Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Human Tumor ◽  
Therapeutic Drug ◽  
Mesenchymal Transition

MiR-375 is a conserved noncoding RNA that is known to be involved in tumor cell proliferation, migration, and drug resistance. Previous studies have shown that miR-375 affects the epithelial-mesenchymal transition (EMT) of human tumor cells via some key transcription factors, such as Yes-associated protein 1 (YAP1), Specificity protein 1 (SP1) -and signaling pathways (Wnt signaling pathway, nuclear factor kappa B (NF-kB) pathway and transforming growth factor β (TGF-β) signaling pathway) and is vital for the development of cancer. Additionally, recent studies have identified miRNA delivery system carriers for improved in vivo transportation of miR-375 to specific sites. Here, we discussed the role of miR-375 in different types of cancers, as well as molecular mechanisms, and analyzed the potential of miR-375 as a molecular biomarker and therapeutic target to improve the efficiency of clinical diagnosis of cancer.

scholarly journals Immunohistological Insight into the Correlation between Neuropilin-1 and Epithelial-Mesenchymal Transition Markers in Epithelial Ovarian Cancer

2014 ◽  
Vol 62 (9) ◽  
pp. 619-631 ◽  
Author(s):  
Sirin A. I. Adham ◽  
Ibtisam Al Harrasi ◽  
Ibrahim Al Haddabi ◽  
Afrah Al Rashdi ◽  
Shadia Al Sinawi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Neuropilin 1 ◽  
Insight Into

scholarly journals Kurarinone Attenuates BLM-Induced Pulmonary Fibrosis via Inhibiting TGF-β Signaling Pathways

2021 ◽  
Vol 22 (16) ◽  
pp. 8388
Author(s):  
Soo-Jin Park ◽  
Tae-hyoun Kim ◽  
Kiram Lee ◽  
Min-Ah Kang ◽  
Hyun-Jae Jang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Lung Epithelial Cells ◽  
Drug Candidate ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
Lung Epithelial ◽  
Novel Drug

Idiopathic pulmonary fibrosis (IPF) is a refractory interstitial lung disease for which there is no effective treatment. Although the pathogenesis of IPF is not fully understood, TGF-β and epithelial–mesenchymal transition (EMT) have been shown to be involved in the fibrotic changes of lung tissues. Kurarinone is a prenylated flavonoid isolated from Sophora Flavescens with antioxidant and anti-inflammatory properties. In this study, we investigated the effect of kurarinone on pulmonary fibrosis. Kurarinone suppressed the TGF-β-induced EMT of lung epithelial cells. To assess the therapeutic effects of kurarinone in bleomycin (BLM)-induced pulmonary fibrosis, mice were treated with kurarinone daily for 2 weeks starting 7 days after BLM instillation. Oral administration of kurarinone attenuated the fibrotic changes of lung tissues, including accumulation of collagen and improved mechanical pulmonary functions. Mechanistically, kurarinone suppressed phosphorylation of Smad2/3 and AKT induced by TGF-β1 in lung epithelial cells, as well as in lung tissues treated with BLM. Taken together, these results suggest that kurarinone has a therapeutic effect on pulmonary fibrosis via suppressing TGF-β signaling pathways and may be a novel drug candidate for pulmonary fibrosis.

Sign in / Sign up

Export Citation Format

Share Document