circPTPN12/miR-21–5 p/∆Np63α pathway contributes to human endometrial fibrosis

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21–5 p to inhibit miR-21–5 p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC–EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC–EMT and administration of miR-21–5 p could reverse this process and improve endometrial fibrosis. Our findings revealed that the dysfunction of circPTPN12/miR-21–5 p/∆Np63α pathway contributed to the pathogenesis of endometrial fibrosis.

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Targeting circPTPN12/1 miR-21-5p/ΔNp63α pathway as a therapeutic strategy for human endometrial fibrosis

10.1101/2021.04.15.440082 ◽

2021 ◽

Author(s):

Minmin Song ◽

Guangfeng Zhao ◽

Haixiang Sun ◽

Simin Yao ◽

Zhenhua Zhou ◽

...

Keyword(s):

Therapeutic Strategy ◽

Epithelial Mesenchymal Transition ◽

Circular Rnas ◽

The Novel ◽

Mesenchymal Transition ◽

Organ Fibrosis ◽

Endometrial Epithelial Cells ◽

Expression And Activity ◽

Uterine Infertility

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21-5p to inhibit miR-21-5p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC-EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC-EMT. Our findings reveal the novel mechanism in the pathogenesis of endometrium fibrosis and the potential therapeutic strategy for endometrium fibrosis via targeting circPTPN12/miR-21-5p/∆Np63α pathway.

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Lipocalin 2 induces the epithelial–mesenchymal transition in stressed endometrial epithelial cells: possible correlation with endometriosis development in a mouse model

Reproduction ◽

10.1530/rep-13-0236 ◽

2014 ◽

Vol 147 (2) ◽

pp. 179-187 ◽

Cited By ~ 17

Author(s):

Chi-Jr Liao ◽

Pei-Tzu Li ◽

Ying-Chu Lee ◽

Sheng-Hsiang Li ◽

Sin Tak Chu

Keyword(s):

Epithelial Cells ◽

Mouse Model ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Lipocalin 2 ◽

Mesenchymal Transition ◽

Endometrial Cells ◽

Cellular Microenvironments ◽

And Migration ◽

Endometrial Epithelial Cells

Lipocalin 2 (LCN2) is an induced stressor that promotes the epithelial–mesenchymal transition (EMT). We previously demonstrated that the development of endometriosis in mice correlates with the secretion of LCN2 in the uterus. Here, we sought to clarify the relationship between LCN2 and EMT in endometrial epithelial cells and to determine whether LCN2 plays a role in endometriosis. Antibodies that functionally inhibit LCN2 slowed the growth of ectopic endometrial tissue in a mouse model of endometriosis, suggesting that LCN2 promotes the formation of endometriotic lesions. Using nutrient deprivation as a stressor, LCN2 expression was induced in cultured primary endometrial epithelial cells. As LCN2 levels increased, the cells transitioned from a round to a spindle-like morphology and dispersed. Immunochemical analyses revealed decreased levels of cytokeratin and increased levels of fibronectin in these endometrial cells, adhesive changes that correlate with induction of cell migration and invasion.Lcn2knockdown also indicated that LCN2 promotes EMT and migration of endometrial epithelial cells. Our results suggest that stressful cellular microenvironments cause uterine tissues to secrete LCN2 and that this results in EMT of endometrial epithelial cells, which may correlate with the development of ectopic endometriosis. These findings shed light on the role of LCN2 in the pathology of endometrial disorders.

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The emerging role of circular RNAs in common solid malignant tumors in children

Cancer Cell International ◽

10.1186/s12935-021-01998-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiabin Yu ◽

Li Yang ◽

Hongting Lu

Keyword(s):

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

Circular Rnas ◽

Development Research ◽

Physical And Mental Health ◽

Invasive Ability ◽

Mesenchymal Transition ◽

Circular Structure ◽

Solid Malignant Tumors

AbstractMalignant tumors are one of the fatal diseases that threaten children’s physical and mental health and affect their development. Research has shown that the occurrence and development of malignant tumors are associated with the abnormal expression and regulation of genes. Circular RNAs (circRNAs) are noncoding RNAs that have a closed circular structure, with a relatively stable expression, and do not undergo exonuclease-mediated degradation readily. Recent studies have shown that circRNA plays an important role in the occurrence, metastasis, and invasion of solid malignant tumors (SMTs) in children. Thus, circRNA is being considered as a breakthrough in the treatment of SMTs in children. In this review, we describe the functions and mechanisms of circRNAs involved in SMTs in children oncogenesis, and summarize the roles of circRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in SMTs in children. In addition, we also discuss the role of circRNAs in the early diagnosis, pathological grading, targeted therapy, and prognosis evaluation of common SMTs in children. CircRNAs are likely to provide a novel direction in therapy in SMTs of children.

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Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Epithelial–Mesenchymal Transition

International Journal of Molecular Sciences ◽

10.3390/ijms20194813 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4813 ◽

Cited By ~ 5

Author(s):

Sevindzh Kletukhina ◽

Olga Neustroeva ◽

Victoria James ◽

Albert Rizvanov ◽

Marina Gomzikova

Keyword(s):

Epithelial Cells ◽

Extracellular Vesicles ◽

Intercellular Communication ◽

Epithelial Mesenchymal Transition ◽

Genetic Material ◽

Biologically Active ◽

Target Cells ◽

Mesenchymal Transition ◽

New Evidence

Epithelial–mesenchymal transition (EMT) is a process that takes place during embryonic development, wound healing, and under some pathological processes, including fibrosis and tumor progression. The molecular changes occurring within epithelial cells during transformation to a mesenchymal phenotype have been well studied. However, to date, the mechanism of EMT induction remains to be fully elucidated. Recent findings in the field of intercellular communication have shed new light on this process and indicate the need for further studies into this important mechanism. New evidence supports the hypothesis that intercellular communication between mesenchymal stroma/stem cells (MSCs) and resident epithelial cells plays an important role in EMT induction. Besides direct interactions between cells, indirect paracrine interactions by soluble factors and extracellular vesicles also occur. Extracellular vesicles (EVs) are important mediators of intercellular communication, through the transfer of biologically active molecules, genetic material (mRNA, microRNA, siRNA, DNA), and EMT inducers to the target cells, which are capable of reprogramming recipient cells. In this review, we discuss the role of intercellular communication by EVs to induce EMT and the acquisition of stemness properties by normal and tumor epithelial cells.

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Role of microRNA-29b in angiotensin II-induced epithelial-mesenchymal transition in renal tubular epithelial cells

International Journal of Molecular Medicine ◽

10.3892/ijmm.2014.1935 ◽

2014 ◽

Vol 34 (5) ◽

pp. 1381-1387 ◽

Cited By ~ 17

Author(s):

JIALIN PAN ◽

JUHONG ZHANG ◽

XINGWEI ZHANG ◽

XI ZHOU ◽

SHENGYUE LU ◽

...

Keyword(s):

Angiotensin Ii ◽

Epithelial Cells ◽

Epithelial Mesenchymal Transition ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Mesenchymal Transition ◽

Renal Tubular

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The Role of the ERK Signaling Pathway on High Glucose-Induced Epithelial-Mesenchymal Transition in Cultured Human Renal Tubular Epithelial Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2018.1758 ◽

2018 ◽

Vol 8 (3) ◽

pp. 405-409

Author(s):

Jian-Rong Zhao ◽

Shan-Shan Xu ◽

Qin Dong ◽

Dong-Ying Shi

Keyword(s):

Epithelial Cells ◽

Signaling Pathway ◽

High Glucose ◽

Epithelial Mesenchymal Transition ◽

Erk Signaling ◽

Tubular Epithelial Cells ◽

Renal Tubular Epithelial Cells ◽

Mesenchymal Transition ◽

Renal Tubular

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TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00163.2007 ◽

2007 ◽

Vol 293 (3) ◽

pp. L525-L534 ◽

Cited By ~ 602

Author(s):

Brigham C. Willis ◽

Zea Borok

Keyword(s):

Epithelial Cells ◽

Lung Disease ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Critical Role ◽

Alveolar Epithelial Cells ◽

Mesenchymal Transition ◽

Fibrotic Lung Disease

Epithelial-mesenchymal transition (EMT), a process whereby fully differentiated epithelial cells undergo transition to a mesenchymal phenotype giving rise to fibroblasts and myofibroblasts, is increasingly recognized as playing an important role in repair and scar formation following epithelial injury. The extent to which this process contributes to fibrosis following injury in the lung is a subject of active investigation. Recently, it was demonstrated that transforming growth factor (TGF)-β induces EMT in alveolar epithelial cells (AEC) in vitro and in vivo, and epithelial and mesenchymal markers have been colocalized to hyperplastic type II (AT2) cells in lung tissue from patients with idiopathic pulmonary fibrosis (IPF), suggesting that AEC may exhibit extreme plasticity and serve as a source of fibroblasts and/or myofibroblasts in lung fibrosis. In this review, we describe the characteristic features of EMT and its mechanistic underpinnings. We further describe the contribution of EMT to fibrosis in adult tissues following injury, focusing especially on the critical role of TGF-β and its downstream mediators in this process. Finally, we highlight recent descriptions of EMT in the lung and the potential implications of this process for the treatment of fibrotic lung disease. Treatment for fibrosis of the lung in diseases such as IPF has heretofore focused largely on amelioration of potential inciting processes such as inflammation. It is hoped that this review will stimulate further consideration of the cellular mechanisms of fibrogenesis in the lung and especially the role of the epithelium in this process, potentially leading to innovative avenues of investigation and treatment.

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