17β-Estradiol mediates TGFBR3/Smad2/3 signaling to attenuate the fibrosis of TGF-β1-induced bovine endometrial epithelial cells via GPER.
E2
GPER
TGF-β1
TGFBR3/Smad2/3 signaling pathway
endometritis
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
22 Nov 2023
22 Nov 2023
Historique:
revised:
11
10
2023
received:
23
03
2023
accepted:
26
10
2023
medline:
22
11
2023
pubmed:
22
11
2023
entrez:
22
11
2023
Statut:
aheadofprint
Résumé
Abnormal function and fibrosis of endometrium caused by cows' endometritis pose difficult implantation of embryos and uterine cavity adhesions. 17β-Estradiol (E2) serves as the most effective aromatized estrogen, and its synthetase and receptors have been detected in the endometrium. Studies have demonstrated the positive role of estrogen in combating pathological fibrosis in diverse diseases. However, it is still unknown whether E2 regulates endometrium fibrosis in bovine endometritis. Herein, we evaluated the expression patterns of transforming growth factor-β1 (TGF-β1), epithelial-mesenchymal transformation (EMT)-related proteins (α-SMA, vimentin N-cadherin and E-cadherin), cytochrome P450 19A1 (CYP19A1), and G protein-coupled estrogen receptor (GPER) in bovine healthy endometrium and Inflammatory endometrium. Our data showed that the inflamed endometrium presented low CYP19A1 and GPER expression, and significantly higher EMT process versus the normal tissue. Moreover, we established a TGF-β1-induced fibrosis model in BEND cells, and found that E2 inhibited the EMT process of BEND cells in a dose-dependent manner. The anti-fibrotic effect of E2 was blocked by the GPER inhibitor G15, but not the estrogen nuclear receptors (ERs) inhibitor ICI182780. Moreover, the GPER agonist G1 inhibited fibrosis and Smad2/3 phosphorylation but increased the expression of TGFBR3 in BEND cells. Transfection with TGFBR3 small interfering RNA blocked the effect of G1 on fibrosis of BEND cells and upregulated the expression of P-Smad2/3. Our in vivo data also showed that E2 and G1 affected uterus fibrosis in mice endometritis model caused by LPS, which was associated with the inhibition of TGFBR3/Smad2/3 signaling. In conclusion, our data implied that E2 alleviates the fibrosis of TGF-β1-induced BEND cells, which is associated with the GPER mediation of TGFBR3/Smad2/3 signaling.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Beijing University of Agriculture Youth Science Innovation Ability Improvement Project
ID : QJKC2022007
Organisme : National Natural Science Foundation of China
ID : 31802263
Organisme : National Natural Science Foundation of China
ID : 32273079
Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
Abudukeyoumu, A., Li, M. Q., & Xie, F. (2020). Transforming growth factor-β1 in intrauterine adhesion. American Journal of Reproductive Immunology, 84, e13262.
Ahn, J. Y., Park, S., Yun, Y. S., & Song, J. Y. (2010). Inhibition of type III TGF-β receptor aggravates lung fibrotic process. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 64, 472-476.
Bonnett, B. N., Miller, R. B., Martin, S. W., Etherington, W. G., & Buckrell, B. C. (1991). Endometrial biopsy in Holstein-Friesian dairy cows. II. Correlations between histological criteria. Canadian journal of veterinary research = Revue canadienne de recherche veterinaire, 55, 162-167.
Caja, L., Dituri, F., Mancarella, S., Caballero-Diaz, D., Moustakas, A., Giannelli, G., & Fabregat, I. (2018). TGF-β and the tissue microenvironment: Relevance in fibrosis and cancer. International Journal of Molecular Sciences, 19, 1294.
Carneiro, L. C., Cronin, J. G., & Sheldon, I. M. (2016). Mechanisms linking bacterial infections of the bovine endometrium to disease and infertility. Reproductive biology, 16, 1-7.
Chevalier, N., Hinault, C., Clavel, S., Paul-Bellon, R., & Fenichel, P. (2021). GPER and testicular germ cell cancer. Frontiers in Endocrinology, 11, 600404.
Eyster, K. M. (2016). The estrogen receptors: An overview from different perspectives. Methods in Molecular Biology, 1366, 1-10.
Fatima, L. A., Campello, R. S., Santos, R. S., Freitas, H. S., Frank, A. P., Machado, U. F., & Clegg, D. J. (2017). Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue. Scientific Reports, 7, 16716.
Fu, K., Shao, L., Mei, L., Li, H., Feng, Y., Tian, W., Huan, Y., & Cao, R. (2021). Tanshinone ⅡA inhibits the lipopolysaccharide-induced epithelial-mesenchymal transition and protects bovine endometrial epithelial cells from pyolysin-induced damage by modulating the NF-κB/Snail2 signaling pathway. Theriogenology, 176, 217-224.
Green, M. P., Ledgard, A. M., Beaumont, S. E., Berg, M. C., McNatty, K. P., Peterson, A. J., & Back, P. J. (2011). Long-term alteration of follicular steroid concentrations in relation to subclinical endometritis in postpartum dairy cows. Journal of Animal Science, 89, 3551-3560.
Hashimoto, Y., Tsuzuki-Nakao, T., Kida, N., Matsuo, Y., Maruyama, T., Okada, H., & Hirota, K. (2023). Inflammatory cytokine-induced HIF-1 activation promotes epithelial-mesenchymal transition in endometrial epithelial cells. Biomedicines, 11, 210.
Henderson, N. C., Rieder, F., & Wynn, T. A. (2020). Fibrosis: from mechanisms to medicines. Nature, 587, 555-566.
Jasiński, T., Zdrojkowski, Ł., Ferreira-Dias, G., Kautz, E., Juszczuk-Kubiak, E., & Domino, M. (2022). Molecular mechanism of equine endometrosis: the NF-κB-dependent pathway underlies the ovarian steroid receptors' dysfunction. International Journal of Molecular Sciences, 23, 7360.
Kaimori, A., Potter, J., Kaimori, J., Wang, C., Mezey, E., & Koteish, A. (2007). Transforming growth factor-β1 induces an epithelial-to-mesenchymal transition state in mouse hepatocytes in vitro. Journal of Biological Chemistry, 282, 22089-22101.
Kolkova, Z., Noskova, V., Ehinger, A., Hansson, S., & Casslen, B. (2010). G protein-coupled estrogen receptor 1 (GPER, GPR 30) in normal human endometrium and early pregnancy decidua. Molecular Human Reproduction, 16, 743-751.
LeBlanc, M. M. (2010). Advances in the diagnosis and treatment of chronic infectious and post-mating-induced endometritis in the mare. Reproduction in Domestic Animals, 45, 21-27.
Liang, H., Zhang, C., Ban, T., Liu, Y., Mei, L., Piao, X., Zhao, D., Lu, Y., Chu, W., & Yang, B. (2012). A novel reciprocal loop between microRNA-21 and TGFβRIII is involved in cardiac fibrosis. The International Journal of Biochemistry & Cell Biology, 44, 2152-2160.
Li, J., Cen, B., Chen, S., & He, Y. (2016). MicroRNA-29b inhibits TGF-β1-induced fibrosis via regulation of the TGF-β1/Smad pathway in primary human endometrial stromal cells. Molecular Medicine Reports, 13, 4229-4237.
Li, Z., Shi, L., Li, Q., Zhao, J., Lu, W., & Wang, J. (2022). The expression and bioinformatics analysis of circular RNAs in endometritis mouse uterus tissues. Molecules, 27, 3682.
Liu, X., Shen, M., Qi, Q., Zhang, H., & Guo, S. W. (2016). Corroborating evidence for platelet-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis. Human Reproduction, 31, 734-749.
Lucas, T. F. G., Siu, E. R., Esteves, C. A., Monteiro, H. P., Oliveira, C. A., Porto, C. S., & Lazari, M. F. M. (2008). 17beta-estradiol induces the translocation of the estrogen receptors ESR1 and ESR2 to the cell membrane, MAPK3/1 phosphorylation and proliferation of cultured immature rat sertoli cells. Biology of Reproduction, 78, 101-114.
Nielsen, C. B., Krag, S., OSterby, R., Flyvbjerg, A., Nyengaard, J., Forman, A., & Wogensen, L. (2004). Transforming growth factor beta1-induced glomerulopathy is prevented by 17beta-estradiol supplementation. Virchows Archiv, 444, 561-566.
Ning, J., Zhang, H., & Yang, H. (2018). MicroRNA−326 inhibits endometrial fibrosis by regulating TGF-β1/Smad3 pathway in intrauterine adhesions. Molecular Medicine Reports, 18, 2286-2292.
Omori, Y., Nakamura, K., Yamashita, S., Matsuda, H., Mizutani, T., Miyamoto, K., & Minegishi, T. (2005). Effect of follicle-stimulating hormone and estrogen on the expression of betaglycan messenger ribonucleic acid levels in cultured rat granulosa cells. Endocrinology, 146, 3379-3386.
Palmisano, B. T., Zhu, L., & Stafford, J. M. (2017). Role of estrogens in the regulation of liver lipid metabolism. Advances in Experimental Medicine and Biology, 1043, 227-256.
Schams, D., & Berisha, B. (2002). Steroids as local regulators of ovarian activity in domestic animals. Domestic Animal Endocrinology, 23, 53-65.
Sheldon, I. M., Lewis, G. S., LeBlanc, S., & Gilbert, R. O. (2006). Defining postpartum uterine disease in cattle. Theriogenology, 65, 1516-1530.
Socha, B. M., Łada, P., Szczepańska, A. A., Łupicka, M., & Korzekwa, A. J. (2018). The influence of experimentally induced endometritis on the PPAR expression profile in the bovine endometrium. Theriogenology, 122, 74-83.
Sun, F., Duan, W., Zhang, Y., Zhang, L., Qile, M., Liu, Z., Qiu, F., Zhao, D., Lu, Y., & Chu, W. (2015). Simvastatin alleviates cardiac fibrosis induced by infarction via up-regulation of TGF-β receptor III expression. British Journal of Pharmacology, 172, 3779-3792.
Wagener, K., Gabler, C., & Drillich, M. (2017). A review of the ongoing discussion about definition, diagnosis and pathomechanism of subclinical endometritis in dairy cows. Theriogenology, 94, 21-30.
Wang, X., Yao, X., Xie, T., Chang, Z., Guo, Y., & Ni, H. (2020). Exosome-derived uterine miR-218 isolated from cows with endometritis regulates the release of cytokines and chemokines. Microbial Biotechnology, 13, 1103-1117.
Wang, Y., Wang, Z., Yu, W., Sheng, X., Zhang, H., Han, Y., Yuan, Z., & Weng, Q. (2018). Seasonal expressions of androgen receptor, estrogen receptors and cytochrome P450 aromatase in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus). European Journal of Histochemistry, 62, 2889.
Wei, T., Chen, W., Wen, L., Zhang, J., Zhang, Q., Yang, J., Liu, H., Chen, B. W., Zhou, Y., Feng, X., Yang, Q., Bai, X., & Liang, T. (2016). G protein-coupled estrogen receptor deficiency accelerates liver tumorigenesis by enhancing inflammation and fibrosis. Cancer Letters, 382, 195-202.
Williams, E. J., Fischer, D. P., Pfeiffer, D. U., England, G. C. W., Noakes, D. E., Dobson, H., & Sheldon, I. M. (2005). Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the immune response in cattle. Theriogenology, 63, 102-117.
Wu, H., Dai, A., Chen, X., Yang, X., Li, X., Huang, C., Jiang, K., & Deng, G. (2018). Leonurine ameliorates the inflammatory responses in lipopolysaccharide-induced endometritis. International Immunopharmacology, 61, 156-161.
Wu, H., Zhao, G., Jiang, K., Chen, X., Rui, G., Qiu, C., Guo, M., & Deng, G. (2016). IFN-τ alleviates lipopolysaccharide-induced inflammation by suppressing NF-κB and MAPKs pathway activation in mice. Inflammation, 39, 1141-1150.
Xiao, L., Wang, Z., Lu, N., He, Y., Qiao, L., Sheng, X., Qi, X., Xing, K., Guo, Y., Chang, D., Wang, X., Zhao, J., Deng, X., Ni, H., & Kang, J. (2022). GPER mediates the IL6/JAK2/STAT3 pathway involved in VEGF expression in swine ovary GCs. Journal of Molecular Endocrinology, 68, 23-33.
Xie, L., Fu, L., Mei, C., Wang, Y., Chen, M., & Gu, X. (2022). Icariin attenuates renal interstitial fibrosis through G protein-coupled estrogen receptor in a UUO murine model. American Journal of Translational Research, 14, 1567-1577.
Yao, Y., Chen, R., Wang, G., Zhang, Y., & Liu, F. (2019). Exosomes derived from mesenchymal stem cells reverse EMT via TGF-β1/Smad pathway and promote repair of damaged endometrium. Stem Cell Research & Therapy, 10, 225.
Yang, Z., Xiao, Z., Guo, H., Fang, X., Liang, J., Zhu, J., Yang, J., Li, H., Pan, R., Yuan, S., Dong, W., Zheng, X. L., Wu, S., & Shan, Z. (2019). Novel role of the clustered miR-23b-3p and miR-27b-3p in enhanced expression of fibrosis-associated genes by targeting TGFBR3 in atrial fibroblasts. Journal of Cellular and Molecular Medicine, 23, 3246-3256.
Zdrojkowski, Ł., Jasiński, T., Ferreira-Dias, G., Pawliński, B., & Domino, M. (2023). The role of NF-κB in endometrial diseases in humans and animals: A review. International Journal of Molecular Sciences, 24, 2901.
Zhou, Z., Wang, H., Zhang, X., Song, M., Yao, S., Jiang, P., Liu, D., Wang, Z., Lv, H., Li, R., Hong, Y., Dai, J., Hu, Y., & Zhao, G. (2022). Defective autophagy contributes to endometrial epithelial-mesenchymal transition in intrauterine adhesions. Autophagy, 18, 2427-2442.
Zralý, Z., Kaláb, P., Canderle, J., Kummer, V., & Raszyk, J. (1989). [Levels of progesterone, 17 beta-estradiol and 11-hydroxycorticosteroid in the blood in cows in different types of puerperal conditions]. Veterinarni Medicina, 34, 515-525.