Expression of Nodal, Cripto, SMAD3, Phosphorylated SMAD3, and SMAD4 in the Proliferative Endometrium of Women With Endometriosis

Cruz, Cynthia Dela; Puerto, Helen L. Del; Rocha, Ana Luiza Lunardi; Cavallo, Ines Katerina Damasceno; Clarizia, Alessandra D.; Reis, Fernando M.

doi:10.1177/1933719114549855

Cited by 17 publications

(13 citation statements)

References 39 publications

(62 reference statements)

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“…Then, the expression changes of TGFB1, SMAD3 and pSMAD3 in epithelial cells were compared between eutopic and normal groups after co-culturing with macrophages. The protein expression levels of TGFB1 and SMAD3 between eutopic and normal endometrium groups differed insignificantly, which is inconsistent with previous studies (Johnson et al 2005, Cruz et al 2015. Another research reported that only weak upregulation of TGFB1 in endometriosis eutopic endometrium occurred compared with the controls (Goteri et al 2015).…”

Section: Discussioncontrasting

confidence: 58%

Different macrophages equally induce EMT in endometria of adenomyosis and normal

An¹,

Dong²,

Yuan³

et al. 2017

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Endometrial cells and microenvironment are two important factors in the pathogenesis of adenomyosis. Our previous study demonstrated that macrophages can induce eutopic epithelial cells of adenomyosis to suffer from epithelial-mesenchymal transition (EMT). The aim of this study is to detect whether macrophages interacting with epithelial cells equally induce the EMT process in normal and eutopic endometria of healthy and adenomyotic patients; and whether macrophages parallelly polarize to M2. We investigated the expression levels of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), cytokeratin7 (CK7), vimentin, transforming growth factor-β1 (TGFB1), SMAD3 and pSMAD3 using immunohistochemistry and western blot, and then estimated the genetic levels of , and using real-time quantitative polymerase chain reaction (RT-PCR) in macrophages. Eutopic and normal endometrial tissues were obtained from 20 patients with adenomyosis and 11 control patients without adenomyosis, respectively. The immunohistochemical analysis shows distinct EMT in eutopic endometria in secretory phase; the expression levels of TGFB1, SMAD3 and pSMAD3 that indicate signal pathway of EMT were also higher in secretory phase. Macrophages can induce EMT process in primary endometrial epithelial cells derived from normal and eutopic endometria. After co-culturing, THP-1-derived macrophages polarized to M2. Compared with the eutopic endometrium group, further polarization to M2 was observed in the normal endometrium group. These results indicate that adenomyosis may be promoted by the pathologic EMT of epithelial cells, which is induced by macrophages that incapably polarize to M2.

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Section: Discussioncontrasting

confidence: 58%

Different macrophages equally induce EMT in endometria of adenomyosis and normal

An¹,

Dong²,

Yuan³

et al. 2017

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“…The cytokine TGF-β is regulated by the JAK-STAT signaling pathway. STAT3 is highly active in the lesions of EMs patients, and TGF-β/Smad signaling pathway plays a key role in tissue fibrosis and has the effect of promoting ectopic endometrial adhesion [18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Exploration of the pathological mechanism of endometriosis in rats using high-throughput sequencing

Miao

Zhen-juan

et al. 2019

Preprint

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Background : This study aimed to explore the pathological mechanism of endometriosis (EMs) in rats by high-throughput sequencing. Methods : Rat EMs model, sham operation group and drug treatment group were established. Uterine tissue was collected for construction of sequencing library and high-throughput sequencing. Data quality was examined. KEGG pathway enrichment analysis was carried out. Results : Percentages of both high-quality sequence Reads and high-quality sequence bases accounted for more than 98%, suggesting that the data quality was acceptable. Total sequences mapped to reference genome (Total Mapped) accounted for more than 90% of total sequences used for mapping (Clean Reads), suggesting that the mapping results of the sequencing data were acceptable. There were 440 differentially expressed genes (DEGs) in the drug treatment group compared with the sham operation group, 382 DEGs in the drug treatment group compared with the model group, and 503 DEGs in the sham operation group compared with the model group. We screened genes ENSRNOG00000023079 and ENSRNOG00000012175 related to vascular endothelial growth factor pathway. The DEGs were mainly enriched in the signaling pathways such as phagosome, natural killer cell mediated cytotoxicity, Janus kinase-signal transducers and activators of transcription signaling pathway, hematopoietic cell lineage, cytokine-cytokine receptor interaction, regulation of actin cytoskeleton and extracellular matrix-receptor interaction. Conclusions : EMs might begin with the inflammatory response of the ectopic endometrium. Phagocytes played a key role in this process. The ectopic endometrium adhered to the abdominal wall with the help of the inflammation reaction, generated blood vessels, and finally transformed into growing lesions.

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“…A decrease in gene expression of cripto was observed in eutopic endometrium of women with endometriosis [5,41,67], but this decrease was not maintained when protein expression was measured [67].…”

Section: The Relationship Between Endometriosis and Tgfb Superfamily mentioning

confidence: 93%

“…Mabuchi et al [66] demonstrated that cells from ovarian endometriosis showed positivity for activin, activin receptors and Smads 2, 3 and 4. We have evaluated the gene expression of Smad 3 and Smad 4, and protein localization of Smad 3, phosphorylated Smad 3 and Smad 4 in eutopic endometrium of women with and without endometriosis, and we found a decrease in Smad 3 in the presence of the disease, however without changes in the distribution of phosphorylated (activated) Smad 3 or in the expression of Smad 4 [67].…”

Section: The Relationship Between Endometriosis and Tgfb Superfamily mentioning

confidence: 95%

“…The gene and protein expression of nodal and cripto [5,41,67] was evaluated in the eutopic endometrium of women with and without endometriosis. A decrease in gene expression of cripto was observed in eutopic endometrium of women with endometriosis [5,41,67], but this decrease was not maintained when protein expression was measured [67].…”

Section: The Relationship Between Endometriosis and Tgfb Superfamily mentioning

confidence: 99%

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The role of TGFβsuperfamily members in the pathophysiology of endometriosis

Cruz

Reis

2015

Gynecological Endocrinology

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The transforming growth factor-beta (TGFβ) superfamily comprises over 30 dimeric proteins with conserved structures, which play important roles in the control of cellular proliferation, differentiation and apoptosis. These proteins are expressed and finely regulated in human endometrium during the menstrual cycle, which is consistent with their effects on endometrial cell proliferation and tissue remodeling. This review is focused on summarizing the role of key members of the TGFβ superfamily in the pathophysiology of endometriosis. Evidence suggests that TGFβ, activins, inhibins, nodal, bone morphogenetic proteins, growth differentiation factors, and anti-Müllerian hormone are produced by endometriotic lesions and could be involved in the establishment and progression of the disease. Their receptors and signaling pathways may also be altered in the presence of endometriosis and may be potential targets to the development of therapeutic agents.

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Expression of Nodal, Cripto, SMAD3, Phosphorylated SMAD3, and SMAD4 in the Proliferative Endometrium of Women With Endometriosis

Cited by 17 publications

References 39 publications

Different macrophages equally induce EMT in endometria of adenomyosis and normal

Different macrophages equally induce EMT in endometria of adenomyosis and normal

Exploration of the pathological mechanism of endometriosis in rats using high-throughput sequencing

The role of TGFβsuperfamily members in the pathophysiology of endometriosis

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