Gene Expression Profiling of the Rat Endometriosis Model

Konno, Ryo; Fujiwara, Hiroyuki; Netsu, Sachiho; Odagiri, Kohei; Shimane, Miyuki; Nomura, Hitoshi; Suzuki, Mitsuaki

doi:10.1111/j.1600-0897.2007.00507.x

Cited by 49 publications

(33 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2) showed expression of LCN2 in mammalian uterine tissue during endometriosis formation. Our findings are consistent with a previous report that showed LCN2 upregulation in a rat model of endometriosis (Konno et al 2007).…”

Section: Discussionsupporting

confidence: 83%

“…As mentioned earlier, LCN2 is upregulated in the endometriotic lesions (Konno et al 2007, Becker et al 2010. We previously found that LCN2 is upregulated in the endometrial carcinoma cells (RL95-2 cells derived from endometrial epithelia) under oxidative stress and that LCN2-induced secreted cytokines trigger cell proliferation and migration (Lin et al 2011).…”

Section: Introductionmentioning

confidence: 99%

“…EMT can be induced by a number of signals, including the acute stress response (Vargha et al 2008). Gene profiling in a rat model of endometriosis identified 71 upregulated and 45 downregulated genes in endometriotic lesions (Konno et al 2007), including an acute-phase protein, lipocalin 2 (LCN2). Thus, LCN2 levels may correlate with EMT and endometriosis onset.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Liao

Lee

et al. 2014

Reproduction

View full text Add to dashboard Cite

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. Lcn2 knockdown 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.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Liao

Lee

et al. 2014

Reproduction

View full text Add to dashboard Cite

show abstract

“…1,2 Global gene expression studies in both human and animal models have shown that endometriotic lesions have aberrant gene expression profiles when compared to normal endometrium. [3][4][5][6][7] The mechanisms at play have not been sufficiently studied, but epigenetic regulation of gene expression is emerging as a key player in endometriosis. 8 Thus, the current knowledge on the pathophysiology of endometriosis supports the involvement of both genetic and epigenetic phenomena in inducing changes in gene expression that lead to disease.…”

Section: Introductionmentioning

confidence: 99%

HDAC1 and HDAC2 are Differentially Expressed in Endometriosis

Colon-Diaz

Báez-Vega

García³

et al. 2012

Reprod. Sci.

View full text Add to dashboard Cite

Epigenetic mechanisms have been ascribed important roles in endometriosis. Covalent histone modifications at lysine residues have been shown to regulate gene expression and thus contribute to pathological states in many diseases. In endometriosis, histone deacetylase inhibition (HDACi) resulted in reactivation of E-cadherin, attenuation of invasion, decreased proliferation of endometriotic cells, and caused lesion regression in an animal model. This study was conducted to assess basal and hormoneregulated gene expression levels of HDAC1 and HDAC2 (HDAC1/2) in cell lines and protein expression levels in tissues. Basal and steroid hormone-regulated HDAC1/2 gene expression levels were determined by quantitative polymerase chain reaction in cell lines and tissues. Protein levels were measured by immunohistochemistry (IHC) in tissues on an endometriosis tissue microarray (TMA). Basal HDAC1/2 gene expression levels were significantly higher in endometriotic versus endometrial stromal cells, which was confirmed by Western blot analysis. Estradiol (E2) and progesterone (P4) significantly downregulated HDAC1 expression in endometrial epithelial cells. Levels of HDAC2 were upregulated by E2 and downregulated by E2 þ P4 in endometrial stromal cells. Hormone modulation of HDAC1/2 gene expression was lost in the endometriotic cell line. Immunohistochemistry showed that HDAC1/2 proteins were expressed in a substantial proportion of lesions and endometrium from patients, and their expression levels varied according to lesion localization. The highest proportion of strong HDAC1 immunostaining was seen in ovarian, skin, and gastrointestinal lesions, and of HDAC2 in skin lesions and endometrium from patients with endometriosis. These studies suggest that endometriosis etiology may be partially explained by epigenetic regulation of gene expression due to dysregulations in the expression of HDACs.

show abstract

“…In rodents, which do not experience menses, endometriosis with proliferating stromal lesions do not occur spontaneously but can be induced by autotransplantation of endometrium (Uchiide et al, 2002). In the endometriosis model induced by autotransplantation of endometrium, enhanced inflammatory reactions and expression of cytokines and chemokines has been reported (Flores et al, 2007;Konno et al, 2007;Umezawa et al, 2008b). Endometriosis in this model is induced within four days post-autotransplantation, peaking at seven days, and declining within 14 days post-surgery (Uchiide et al, 2002).…”

Section: Discussionmentioning

confidence: 95%

Pathological study for the effects of in utero and postnatal exposure to diesel exhaust on a rat endometriosis model

et al. 2011

View full text Add to dashboard Cite

-Previous studies have shown that prenatal and postnatal exposure to diesel exhaust (DE), which is known to be one of the main constituents of air pollution, enhances the persistence of endometriosis in a rat model. The aim of this study is to investigate the pathological changes induced by DE exposure in a rat model of endometriosis. Pregnant Sprague-Dawley rats were exposed to DE or clean air beginning on gestational day 2 and neonatal rats were persistently exposed to DE or clean air. Endometriosis was induced by autotransplantation of endometrium onto the peritoneum of eight-week-old female offspring. Endometriotic lesions were examined at 7 and 14 days post-transplantation. As a result, infiltration of activated mast cells remained in deeper area of peritoneal tissue around the endometriosis model compared to the control group at 14 days post-autotransplantation. In the DE exposure group, 14 days post-transplant, the remaining lesions contained fibroblasts and activated mast cells, which were surrounded by collagen fibers. The data showed that prenatal and postnatal DE exposure enhances the activation of mast cells and prolongs the persistence of collagen fibers in the induced rat model of endometriosis.

show abstract

Gene Expression Profiling of the Rat Endometriosis Model

Abstract: The results suggest that osteopontin, Lyn, Vav1, Runx1, and l-selectin play important roles in the pathogenesis of endometriosis.

Cited by 49 publications

References 53 publications

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

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

HDAC1 and HDAC2 are Differentially Expressed in Endometriosis

Pathological study for the effects of in utero and postnatal exposure to diesel exhaust on a rat endometriosis model

Contact Info

Product

Resources

About