Biology of Eutopic and Ectopic Endometrium in Women with Endometriosis

Klemmt, Petra; Starzinski‐Powitz, Anna

doi:10.1002/9781444398519.ch11

Cited by 2 publications

(2 citation statements)

References 159 publications

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“…Endometriosis is a condition where the lining of the uterus grows at ectopic locations, such as the ovaries and the peritoneum, causing severe pain and subfertility [9]. While the exact causes of the disease remain unknown, several studies confirmed that the phenotype of endometrial ectopic cells differs from that found in eutopic endometrium [1] [10] [11] [12] For example, ectopic endometrial cells are progesterone resistant [13], can produce estrogen [14], are contractile [15] and invasive [16]. This could be due to several factors, including altered microRNA expression and its associated posttranscriptional regulation of microRNA targets in the ectopic milieu [17] [18] [19].…”

Section: Introductionmentioning

confidence: 99%

miR-142-3p Reduces the Size, Migration and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-related Pathways that Regulate Cytoskeletal Function

Börschel¹,

Stejskalová²,

Schäfer³

et al. 2020

Preprint

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Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis [1] [2], an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates ROCK2, CFL2, RAC1, WASL and ITGAV. qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.

show abstract

Section: Introductionmentioning

confidence: 99%

miR-142-3p Reduces the Size, Migration and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-related Pathways that Regulate Cytoskeletal Function

Börschel¹,

Stejskalová²,

Schäfer³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Endometriosis is a condition where the lining of the uterus grows at ectopic locations, such as the ovaries and the peritoneum, causing severe pain and subfertility [8]. While the exact causes of the disease remain unknown, several studies confirmed that the phenotype of endometrial ectopic cells differs from that found in eutopic (eut) endometrium [5,[9][10][11]. For example, ectopic (ect) endometrial cells are progesterone resistant [12], can produce estrogen [13], are contractile [14] and invasive [15].…”

Section: Introductionmentioning

confidence: 99%

miR-142-3p Reduces the Size, Migration, and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-Related Pathways That Regulate Cytoskeletal Function

et al. 2020

View full text Add to dashboard Cite

Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis, an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates Rho-associated protein kinase 2 (ROCK2), cofilin 2 (CFL2), Ras-related C3 botulinum toxin substrate 1 (RAC1), neural Wiskott-Aldrich syndrome protein (WASL), and integrin α-V (ITGAV). qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters, and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.

show abstract

Biology of Eutopic and Ectopic Endometrium in Women with Endometriosis

Cited by 2 publications

References 159 publications

miR-142-3p Reduces the Size, Migration and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-related Pathways that Regulate Cytoskeletal Function

miR-142-3p Reduces the Size, Migration and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-related Pathways that Regulate Cytoskeletal Function

miR-142-3p Reduces the Size, Migration, and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-Related Pathways That Regulate Cytoskeletal Function

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