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      Immunoreactivity of Plasminogen Activator Inhibitor 1 and Its Correlation with Dysmenorrhea and Lesional Fibrosis in Adenomyosis

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          Abstract

          Adenomyosis is associated with dysmenorrhea, infertility, and lesional fibrosis. The pathogenesis of adenomyosis is still unclear. Plasminogen activator inhibitor 1 (PAI-1) plays important roles in pathological activities like tumor metastasis and endometriosis. Our objective was to investigate the expression and localization of PAI-1 in eutopic and ectopic endometrium with adenomyosis and in endometrium without adenomyosis. We also sought to determine the relationship between PAI-1 immunoreactivity and the severity of dysmenorrhea and the extent of lesional fibrosis in adenomyosis. PAI-1 expression was significantly higher in the ectopic endometrium of patients with adenomyosis than in both the eutopic endometrium of patients with adenomyosis and the endometrium of controls. Ectopic PAI-1 expression correlated positively with dysmenorrhea visual analog scale (VAS) scores and the extent of lesional fibrosis in adenomyosis. High PAI-1 expression increased the likelihood of moderate to severe dysmenorrhea in adenomyosis. These results suggest that PAI-1 is involved in the adenomyosis-associated dysmenorrhea and lesional fibrosis, which provide a potential target in treating symptomatic adenomyosis.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s43032-021-00513-6.

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          Most cited references33

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          Angiogenesis in cancer and other diseases.

          Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases. Concentrated efforts in this area of research are leading to the discovery of a growing number of pro- and anti-angiogenic molecules, some of which are already in clinical trials. The complex interactions among these molecules and how they affect vascular structure and function in different environments are now beginning to be elucidated. This integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases. But owing to several unanswered questions, caution is needed.
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            The plasminogen activation system in tumor growth, invasion, and metastasis.

            Generation of the serine proteinase plasmin from the extracellular zymogen plasminogen can be catalyzed by either of two other serine proteinases, the urokinase- and tissue-type plasminogen activators (uPA and tPA). The plasminogen activation system also includes the serpins PAI-1 and PAI-2, and the uPA receptor (uPAR). Many findings, gathered over several decades, strongly suggest an important and causal role for uPA-catalyzed plasmin generation in cancer cell invasion through the extracellular matrix. Recent evidence suggests that the uPA system is also involved in cancer cell-directed tissue remodeling. Moreover, the system also supports cell migration and invasion by plasmin-independent mechanisms, including multiple interactions between uPA, uPAR, PAI-1, extracellular matrix proteins, integrins, endocytosis receptors, and growth factors. These interactions seem to allow temporal and spatial reorganizations of the system during cell migration and a selective degradation of extracellular matrix proteins during invasion. The increased knowledge about the plasminogen activation system may allow utilization of its components as targets for anti-invasive therapy.
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              Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization.

              Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. High levels of components of the plasminogen activation system, including urokinase, but paradoxically also its inhibitor, plasminogen activator inhibitor 1 (PAI1), have been correlated with a poor prognosis for some cancers. We report here that deficient PAI1 expression in host mice prevented local invasion and tumor vascularization of transplanted malignant keratinocytes. When this PAI1 deficiency was circumvented by intravenous injection of a replication-defective adenoviral vector expressing human PAI1, invasion and associated angiogenesis were restored. This experimental evidence demonstrates that host-produced PAI is essential for cancer cell invasion and angiogenesis.
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                Author and article information

                Contributors
                ybx1995@sjtu.edu.cn
                marcogoo@sjtu.edu.cn
                wendyshishu@163.com
                13916681426@163.com
                lanzchen@163.com
                ouyangjing126@126.com
                linyu089@163.com
                sunfeng0711@126.com
                xuhong1558@sjtu.edu.cn
                Journal
                Reprod Sci
                Reprod Sci
                Reproductive Sciences
                Springer International Publishing (Cham )
                1933-7191
                1933-7205
                8 March 2021
                8 March 2021
                August 2021
                : 28
                : 8
                : 2378-2386
                Affiliations
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, International Peace Maternity and Child Health Hospital, School of Medicine, , Shanghai Jiao Tong University, ; NO. 910, Heng-Shan Road, Xu-Hui Qu, Shanghai, 200030 China
                [2 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Shanghai Key Laboratory of Embryo Original Diseases, ; Shanghai, 200030 China
                Author information
                http://orcid.org/0000-0003-0314-9145
                Article
                513
                10.1007/s43032-021-00513-6
                8289782
                33683668
                d834b595-2a73-4d81-aa26-3c2147fcde2c
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 November 2020
                : 21 February 2021
                Funding
                Funded by: National Key Research and Development Program of China
                Award ID: 2020YFC2002804
                Award Recipient :
                Funded by: Shanghai Municipal Key Clinical Specialty
                Award ID: shslczdzk01802
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81771551
                Award ID: 81901536
                Award ID: 81701402
                Award Recipient :
                Funded by: Shanghai Chinese Traditional and Western Medicine Clinical Collaboration Pilot Construction Project
                Award ID: ZXYXZ-201905
                Award Recipient :
                Funded by: Research Program of International Peace Maternal and Child Health Hospital
                Award ID: CR2018WX06
                Award ID: YN201914
                Award Recipient :
                Funded by: Shanghai Shenkang Hospital Development Center Clinical Science and Technology Innovation Project
                Award ID: SHDC12017123
                Award Recipient :
                Categories
                Adenomyosis: Original Article
                Custom metadata
                © Society for Reproductive Investigation 2021

                adenomyosis,pai-1,immunohistochemistry,dysmenorrhea,fibrosis

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