The extracellular signal‐regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation

Arlıer, Sefa; Murk, William; Guzeloglu‐Kayisli, Ozlem; Semerci, Nihan; Larsen, Kellie; Tabak, Mehmet Selcuk; Arıcı, Aydın; Schatz, Frederick; Lockwood, Charles J.; Kayisli, Umit A.

doi:10.1111/aji.12760

Cited by 12 publications

(15 citation statements)

References 42 publications

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“…It can be explained that which signals or signaling pathways leads the endometrial cells to migrate, implant, grow, invade, and create a microenvironment. Since the MAPK signaling pathway crosstalk with the immune system elements and play role in angiogenesis, it is also possible to gain insight into the microenvironment that they create for their survival at the site of involvement 42, 64, 65 . Studies on the link between endometriosis and MAPK signaling pathway will provide more insight into the underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…65 This study which is very important for interpretation of the pro-angiogenic microenvironment in endometriosis showed that ERK signaling pathway activation is one of the triggers of human ectopic endometrial angiogenesis which might lead the severity of disease. 65 The correlation between Bcl-2, CD147 and ERK signaling pathway in human endometriosis was showed and reported that the activation of ERK signaling pathway in endometriotic lesions leads to the Bcl-2 activation which is a suppressor of intrinsic apoptosis pathway. The role of the ERK signaling pathway in reduced apoptosis and so enhanced cell survival in human endometriosis was showed.…”

Section: Erk Mapk Signaling Pathwaymentioning

confidence: 94%

“…In another study on the role of ERK signaling pathway in endometriosis reported that angioblasts in endometriotic lesions show increased ERK1/2 activation 65 . This study which is very important for interpretation of the pro‐angiogenic microenvironment in endometriosis showed that ERK signaling pathway activation is one of the triggers of human ectopic endometrial angiogenesis which might lead the severity of disease 65 . The correlation between Bcl‐2, CD147 and ERK signaling pathway in human endometriosis was showed and reported that the activation of ERK signaling pathway in endometriotic lesions leads to the Bcl‐2 activation which is a suppressor of intrinsic apoptosis pathway.…”

Section: Endometriosismentioning

confidence: 98%

“…In the study conducted with both human endometrial and ectopic endometrial cell cultures and also mouse model; it is reported that the size of the endometriotic lesion decreased and ERK signaling pathway might activate through VEGFR and cause the growth of endometriotic lesions by effecting angiogenesis 64 . In another study on the role of ERK signaling pathway in endometriosis reported that angioblasts in endometriotic lesions show increased ERK1/2 activation 65 . This study which is very important for interpretation of the pro‐angiogenic microenvironment in endometriosis showed that ERK signaling pathway activation is one of the triggers of human ectopic endometrial angiogenesis which might lead the severity of disease 65 .…”

Section: Endometriosismentioning

confidence: 99%

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The role of mitogen‐activated protein kinase signaling pathway in endometriosis

Bora

Yaba

2021

J of Obstet and Gynaecol

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Aim Endometriosis is an estrogen‐dependent chronic inflammatory condition which causes pain, infertility, and predisposition for ovarian cancer. Endometriosis generates a unique microenvironment for survivability of endometriotic lesions which includes cell proliferation, differentiation, migration, and apoptosis. For these cellular activities, cascading activations of intracellular kinases are needed. Many kinase signaling pathways, IKKβ/NK‐κB pathway, PI3K/AKT/mTOR, and the mitogen‐activated protein kinase (MAPK) pathways (ERK1/2, p38, and JNK), are activated in endometriosis. In this review, we focus on the role of MAPK pathways in endometriosis. Methods To identify the role of MAP Kinase signaling pathway in endometriosis we searched the Pubmed database using the search terms in various combinations “endometriosis,” “endometrium,” “ovary,” “MAPK pathway,” “ERK pathway,” “p38 pathway,” “JNK pathway,” “estrogen,” and “progesterone.” Results According to the current literature, MAPK signaling pathway has various roles in generating microenvironment and survival of endometriosis. Abnormal MAPK activation in migration, implantation, growth, invasion into the pelvic structures, proliferation, and apoptosis leads to the form of endometriosis and to worsen the condition in patients with endometriosis. Conclusion To further investigations on the effective and long‐term endometriosis treatment, MAPK signaling pathways may be targeted. Molecular mechanism of MAPK signaling pathway in endometriosis should be more deeply understood and clinical trials should be more commonly performed for possible new endometriosis treatments to improve fertility and rescue endometriosis irreversibly.

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Section: Discussionmentioning

confidence: 99%

Section: Erk Mapk Signaling Pathwaymentioning

confidence: 94%

Section: Endometriosismentioning

confidence: 98%

Section: Endometriosismentioning

confidence: 99%

See 2 more Smart Citations

The role of mitogen‐activated protein kinase signaling pathway in endometriosis

Bora

Yaba

2021

J of Obstet and Gynaecol

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“…The mobility, EMT and proliferation of human It is reported that the level of phosphorylated ERK was significantly higher in endometriotic lesions than in endometrial tissues. 31,32 And the activated ERK regulated over 160 proteins, which involved with the cell proliferation, apoptosis, angiogenesis and migration in endometriosis. [33][34][35] As exhibited in previous results, oes- transcriptional activities in cells.…”

Section: Discussionmentioning

confidence: 99%

RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis

Huang

Mao

et al. 2020

J Cellular Molecular Medi

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Endometriosis is a benign gynaecological disease appearing with pelvic pain, rising dysmenorrhoea and infertility seriously impacting on 10% of reproductive‐age females. This research attempts to demonstrate the function and molecular mechanism of RhoA/ROCK pathway on epithelial‐mesenchymal transition (EMT) and proliferation in endometriosis. The expression of Rho family was abnormally changed in endometriotic lesions; in particular, RhoA and ROCK1/2 were significantly elevated. Overexpression of RhoA in human eutopic endometrial epithelial cells (eutopic EECs) enhanced the cell mobility, epithelial‐mesenchymal transition (EMT) and proliferation, and RhoA knockdown exhibited the opposite function. Oestrogen up‐regulated the RhoA activity and expression of RhoA and ROCK1/2. RhoA overexpression reinforced the effect of oestrogen on promoting EMT and proliferation, and RhoA knockdown impaired the effect of oestrogen. oestrogen receptor α (ERα) was involved with the regulation of oestrogen on EMT and proliferation and up‐regulated RhoA activity and expression of RhoA and ROCK1/2. The function of ERα was modulated by the change in RhoA expression. Furthermore, phosphorylated ERK that was enhanced by oestrogen and ERα promoted the protein expression of RhoA/ROCK pathway. Endometriosis mouse model revealed that oestrogen enhanced the size and weight of endometriotic lesions. The expression of RhoA and phosphorylated ERK in mouse endometriotic lesions was significantly elevated by oestrogen. We conclude that abnormal activated RhoA/ROCK pathway in endometriosis is responsible for the function of oestrogen/ERα/ERK signalling, which promoted EMT and proliferation and resulted in the development of endometriosis.

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Transcriptome sequencing of endometrium revealed alterations in mRNAs and lncRNAs after ovarian stimulation

Wang

Liu

et al. 2019

J Assist Reprod Genet

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Research question Using RNA-sequencing analysis, we investigated the relationship between ovarian stimulation and endometrial transcriptome profiles during the window of implantation (WOI) to identify candidate predictive factors for the WOI and to optimize timing for embryo transfer. Methods Twelve women with normal basal hormone levels and regular ovulation were randomly assigned into three groups based on sampling time: late-proliferate phase (P group), and receptive phase in natural cycles (LH+7, N group) and stimulated cycles (hCG+7, S group). Transcriptome profiles of mRNAs and long non-coding RNAs (lncRNAs) were then compared among the three groups. Validation was performed using real-time qPCR. Results Comparison of transcriptome profiles between the natural and stimulated endometrium revealed 173 differentially expressed genes (DEGs), with a > 2-fold change (FC) and p < 0.05, under the influence of supraphysiological estradiol (E 2 ) induced by ovarian stimulation. By clustering and KEGG pathway analysis, molecules and pathways associated with endometrial receptivity were identified. Of the 39 DEGs common to the three groups, eight genes were validated using real-time PCR. ESR1, MMP10, and HPSE were previously reported to be associated with endometrial receptivity. In addition, three novel genes (IL13RA2, ZCCHC12, SRARP) and two lncRNAs (LINC01060, LINC01104) were new potential endometrial receptivity-related markers. Conclusion Using mRNA and lncRNA sequencing, we found that supraphysiological E 2 levels from ovarian stimulation had a marked impact upon endometrial transcriptome profiles and may result in a shift of the WOI. The precise mechanisms underlying the supraphysiological hormone-induced shift of the WOI require further research. Registration number ChiCTR180001453

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The extracellular signal‐regulated kinase 1/2 triggers angiogenesis in human ectopic endometrial implants by inducing angioblast differentiation and proliferation

Abstract: Enhanced ERK1/2 activity in angioblasts by such peritoneal factors as VEGF, E induces proliferation to trigger ectopic endometrial angiogenesis.

Cited by 12 publications

References 42 publications

The role of mitogen‐activated protein kinase signaling pathway in endometriosis

The role of mitogen‐activated protein kinase signaling pathway in endometriosis

RhoA/ROCK pathway mediates the effect of oestrogen on regulating epithelial‐mesenchymal transition and proliferation in endometriosis

Transcriptome sequencing of endometrium revealed alterations in mRNAs and lncRNAs after ovarian stimulation

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