The role of TGF<b>β</b>superfamily members in the pathophysiology of endometriosis

Cruz, Cynthia Dela; Reis, Fernando M.

doi:10.3109/09513590.2015.1018166

Cited by 24 publications

(21 citation statements)

References 64 publications

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“…The expression of these integrins is tightly regulated by diverse molecules, such as interleukin (IL)-1, IL-8, macrophage inhibitory factor (MiR)-183, prostaglandin E2, and a cannabinoid receptor agonist ( 7 , 9 – 11 , 37 , 38 ). However, despite the obvious importance of TGF-β1 in the progression of endometriosis ( 13 , 17 ), there have been no reports of the TGF-β1 function in the regulation of integrins in endometrial cells. Thus, we examined the regulation of integrins by TGF-β1 and their role in the initiation of endometriosis.…”

Section: Discussionmentioning

confidence: 99%

“…In human endometriosis lesions, TGF-β1 expression has been found in macrophages, endometrial epithelial cells, endometrial stromal cells, and mesothelial cells ( 13 , 24 ). Elevated levels of secreted TGF-β1 in peritoneal fluid influenced many steps in the progression of endometriosis, including immune surveillance, cell adhesion and invasion into the peritoneum, angiogenesis, and growth of implants ( 13 , 17 ). The response of TGF-β1 measured by endometrial-mesothelial adhesion is different between normal endometrial HES cells and ectopic endometrial cells (12Z).…”

Section: Discussionmentioning

confidence: 99%

“…TGF-β expression is higher in the serum, peritoneal fluid, and cyst tissues of patients with endometriosis than in women without endometriosis ( 14 – 16 ). Among the three subtypes of TGF-βs, TGF-β1 is generally considered to be a key player in the pathogenesis of endometriosis, due to its pattern of expression and correlation with disease progression ( 13 , 17 ). TGF-β1 is involved in the suppression of immune surveillance, cell adhesion and invasion into the peritoneum, and in the growth of implants ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

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Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

et al. 2017

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Endometriosis is the abnormal growth of endometrial cells outside the uterus, causing pelvic pain and infertility. Furthermore, adhesion of endometrial tissue fragments to pelvic mesothelium is required for the initial step of endometriosis formation outside uterus. TGF-β1 and adhesion molecules importantly function for adhesion of endometrial tissue fragments to mesothelium outside uterus. However, the function of TGF-β1 on the regulation of adhesion molecule expression for adhesion of endometrial tissue fragments to mesothelium has not been fully elucidated. Interestingly, transforming growth factor β1 (TGF-β1) expression was higher in endome-triotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to meso-thelial cells was also higher than that of normal endometrial cells. Moreover, TGF-β1 directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of αV, α6, β1, and β4 via the activation of the TGF-β1/TGF-βRI/Smad2 signaling pathway. Conversely, the adhesion of TGF-β1-stimulated endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific TGF-β1-mediated integrins αV, β1, and β4 on the endometrial cell membrane. Taken together, these results suggest that TGF-β1 may act to promote the initiation of endometriosis by enhancing integrin-mediated cell-cell adhesion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

et al. 2017

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“…The increased secretion of inflammatory cytokines [7], chemokines [93], and growth factors [94, 95] in endometriosis has been widely demonstrated. Although the presence of endometriotic pain is mostly associated with the disease progression [96], the generation of the pain in endometriosis remains unknown.…”

Section: Macrophage and Nerve Interaction In Endometriosismentioning

confidence: 99%

Macrophage and nerve interaction in endometriosis

Xie

Yao

et al. 2017

J Neuroinflammation

119

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Dysregulation of the immune system in endometriotic milieus has been considered to play a pivotal role in the pathogenesis of endometriosis. Macrophage recruitment and nerve fiber infiltration are the two major characteristics of this aberrant immune environment. First, the recruitment of macrophages and their polarization phenotype within the endometriotic lesion have been demonstrated to facilitate the development and maintenance of endometriosis. M1 phenotype of macrophages has the capacity to secrete multiple cytokines for inflammatory response, while M2 macrophage possesses an opposite property that can mediate the process of immunosuppression and neuroangiogenesis. Upon secretion of multiple abnormal signal molecules by the endometriotic lesion, macrophages could alter their location and phenotype. These changes facilitate the accommodation of the aberrant microenvironment and the exacerbation of disease progression. Second, the infiltration of nerve fibers and their abnormal distribution are proved to be involved in the generation of endometriosis-associated pain and inflammatory response. An imbalance in sensory and sympathetic innervation and the abnormal secretion of different cytokines could mediate neurogenesis and subsequent peripheral neuroinflammation in endometriosis. Although endometriosis creates an inflammatory milieu promoting macrophage infiltration and an imbalanced innervation, interaction between macrophages and nerve fibers in this process remains unknown. The aim of this review is to highlight the role of macrophage and nerve interaction in endometriosis, where macrophage recruitment and neurogenesis can be the underlying mechanism of neuroinflammation and pathogenesis of endometriosis.

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“…We found that the NF‐κBp50 inhibitor, SN50, decreased the expression of CD36 and SIRP‐α in macrophages that were treated with normal but not eutopic endometrial homogenate, suggesting the involvement of different macrophage regulatory mechanisms between normal and eutopic endometrium. Previous evidence has demonstrated increased levels of TGF‐β in eutopic and ectopic endometrial lesions, accompanied by decreased immune cell activity within the peritoneum, further fuelling EM lesion development . Han et al reported that TGF‐β1/2 significantly decreases the expression of CD36 in macrophages through a mechanism that involves phosphorylation of mitogen‐activated protein kinase .…”

Section: Discussionmentioning

confidence: 99%

Eutopic endometrium from patients with endometriosis modulates the expression of CD36 and SIRP‐α in peritoneal macrophages

Xie

et al. 2019

J of Obstet and Gynaecol

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Aim This study aimed to investigate the in vitro alterations of the expression of signal regulatory protein‐α (SIRP‐α) and CD36 in macrophages in the endometriosis condition. Methods The expression of SIRP‐α and CD36 was measured in peritoneal macrophages and peripheral blood mononuclear cells of endometriosis patients and control participants. The expressions of SIRP‐α and CD36 were measured in human acute monocytic leukemia (THP‐1) cell‐derived macrophages that were treated with interleukin‐6 (IL‐6)‐induced conditioned medium, eutopic versus normal endometrial homogenate, or lipopolysaccharide in the presence or absence of nuclear factor kappa‐B (NF‐κB) or transforming growth factor (TGF‐β) inhibitors, respectively. Results Peritoneal macrophages that were isolated from women with endometriosis exhibited an enhanced expression of SIRP‐α and a decreased expression of CD36 compared to control participants. Women with endometriosis had significantly higher levels of SIRP‐α and CD36 in peripheral circulating mononuclear cells than in control participants. SIRP‐α expression was significantly increased, whereas the CD36 expression was decreased in THP‐1 cell‐derived macrophages after treatment with eutopic endometrial homogenate. Intervention with IL‐6‐induced conditioned medium resulted in the downregulation of SIRP‐α but the upregulation of CD36 in THP‐1 cells. Incubation with the NF‐κBp50 inhibitor decreased the expression of CD36 and SIRP‐α in macrophages that were treated with normal endometrial homogenate, whereas the TGF‐β inhibitor enhanced the CD36 expression of THP‐1 cell‐derived macrophages treated with eutopic endometrial homogenate. Conclusion The eutopic endometrium could reduce the phagocytic ability of peritoneal macrophages in women with endometriosis through the modulation of SIRP‐α and CD36 expression. Inhibition of the TGF‐β signal pathway may be a potential therapeutic target for the treatment of endometriosis.

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The role of TGFβsuperfamily members in the pathophysiology of endometriosis

Cited by 24 publications

References 64 publications

Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

Macrophage and nerve interaction in endometriosis

Eutopic endometrium from patients with endometriosis modulates the expression of CD36 and SIRP‐α in peritoneal macrophages

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