Cyclic Stretch Augments Production of Neutrophil Chemokines, Matrix Metalloproteinases, and Activin A in Human Endometrial Stromal Cells

2015 ◽  
Vol 73 (6) ◽  
pp. 501-506 ◽  
Author(s):  
Gentaro Izumi ◽  
Kaori Koga ◽  
Miwako Nagai ◽  
Yoko Urata ◽  
Masashi Takamura ◽  
...  
Endocrinology ◽  
2021 ◽  
Author(s):  
Kazuya Kusama ◽  
Yuta Fukushima ◽  
Kanoko Yoshida ◽  
Mana Azumi ◽  
Mikihiro Yoshie ◽  
...  

Abstract Endometriosis is characterized by inflammation and fibrotic changes. Our previous study using a mouse model showed that proinflammatory factors present in peritoneal hemorrhage exacerbated inflammation in endometriosis-like grafts, at least in part through the activation of prostaglandin (PG) E2 receptor and protease-activated receptor (PAR). In addition, menstruation-related factors, PGE2 and thrombin, a PAR1 agonist (P/T) induced epithelial-mesenchymal transition (EMT) of endometrial cells under hypoxia. However, the molecular mechanisms by which P/T induce development of endometriosis have not been fully characterized. To investigate the effects of P/T, RNA extracted from endometrial stromal cells (ESCs) treated with P/T were subjected to RNA sequence analysis, and identified activin A, FOS, GATA2 as upregulated genes. Activin A increased the expression of connective tissue growth factor (CTGF) and mesenchymal marker genes in ESCs. CTGF induced the expression of fibrosis marker type I collagen, fibronectin, and α-smooth muscle actin (αSMA), indicating fibroblast to myofibroblast transdifferentiation (FMT) of ESCs. In addition, activin A, FOS, GATA2, CTGF, and αSMA were localized in endometriosis lesions. Taken together, our data show that P/T induce changes resembling EMT and FMT in ectopic ESCs derived from retrograde menstruation, and that these are associated with fibrotic changes in the lesions. Pharmacological means that block P/T-induced activin A and CTGF signaling may be strategies to inhibit fibrosis in endometriotic lesions.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Juan Zheng ◽  
Juan Qu ◽  
Pinhong Lu ◽  
Zhen Hou ◽  
Yugui Cui ◽  
...  

Endometriosis is an estrogen-dependent disease. We previously found that the expression of Activin A was upregulated in the peritoneal fluid of patients with endometriosis. The results of the present study indicated that Activin A induced estradiol secretion and P450arom expression in endometrial stromal cells (ESCs) derived from endometriosis patients. The mechanism of estrogenic synthesis was regulated by the Activin-Smad pathway in endometrial lesions. The data showed that the effect of Activin A on ESCs was partially abrogated by pretreatment with an inhibitor of ALK4 (the type I receptor, ActRIB) and Smad4-siRNA. Cumulatively, these data suggest that Activin A promotes the secretion of estradiol from ESCs by increasing the expression of P450arom via the ALK4-Smad pathway. These findings indicate the ALK4-Smad pathway may promote ectopic lesion survival and development.


2007 ◽  
Vol 14 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Pasquale Florio ◽  
Marco Rossi ◽  
Paola Viganò ◽  
Stefano Luisi ◽  
Michela Torricelli ◽  
...  

2015 ◽  
Vol 32 (2) ◽  
pp. 161-165 ◽  
Author(s):  
Larissa M. Coutinho ◽  
Erica L. Vieira ◽  
Cynthia Dela Cruz ◽  
Maíra Casalechi ◽  
Antonio L. Teixeira ◽  
...  

2006 ◽  
Vol 290 (2) ◽  
pp. E268-E272 ◽  
Author(s):  
Miyuki Harada ◽  
Yutaka Osuga ◽  
Yuri Takemura ◽  
Osamu Yoshino ◽  
Kaori Koga ◽  
...  

Decidualization is an essential process of endometrial differentiation for embryo implantation and maintenance of pregnancy. Recently, uterine movement-induced mechanical stress was noticed to have possible effects on endometrial functions. In this study, we addressed the possible effect of mechanical stress on the process of decidualization of endometrial stromal cells (ESC). ESC were cultured on flexible-bottomed culture plates. After decidualization was achieved with estradiol and progesterone for 12 days, cultures were continued for 24 h with or without cyclic stretch (25% elongation) in serum-free conditions at a rate of 2 cycles/min using a computer-operated cell tension system. Concentrations of insulin-like growth factor-binding protein-1 (IGFBP-1), a marker of decidualization, in the conditioned medium were measured by specific ELISA, and IGFBP-1 mRNA expression in the ESC was measured by RT-PCR. Cyclic stretch remarkably increased IGFBP-1 secretion from decidualized ESC. It also increased IGFBP-1 mRNA in decidualized ESC. The increase in IGFBP-1 secretion was inhibited by actinomycin D but not by indomethacin, PD-98059, or H-89. Conditioned medium of decidualized ESC cultured with cyclic stretch increased IGFBP-1 secretion from decidualized ESC cultured under stationary conditions. These findings imply that uterine movement modulates decidualization of the endometrium and has a regulatory effect on reproduction.


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