Role of Plasminogen Activator Inhibitor Type 1 in Pathologies of Female Reproductive Diseases

Yao, Ye; Vattai, Aurelia; Zhang, Xi; Zhu, Jianjun; Thaler, Christian J.; Mahner, Sven; Jeschke, Udo; Schönfeldt, Viktoria von

doi:10.3390/ijms18081651

Cited by 78 publications

(40 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, significantly increased levels of PAI-1 produced by senescent ESCs, may not only be responsible for triggering paracrine senescence in the neighboring cells, but also, may play role in the prevention of trophoblast invasion mediating various reproductive diseases. Indeed, it was shown that elevated levels of PAI-1 accompany such pathologies as recurrent pregnancy loss, repeated implantation failures and unexplained female infertility [42, 45, 46].…”

Section: Discussionmentioning

confidence: 99%

Molecular basis of senescence transmitting in the population of human endometrial stromal cells

Griukova

Deryabin

Shatrova

et al. 2019

Aging

View full text Add to dashboard Cite

Hormone-regulated proliferation and differentiation of endometrial stromal cells (ESCs) determine overall endometrial plasticity and receptivity to embryos. Previously we revealed that ESCs may undergo premature senescence, accompanied by proliferation loss and various intracellular alterations. Here we focused on whether and how senescence may be transmitted within the ESCs population. We revealed that senescent ESCs may induce paracrine senescence in young counterparts via cell contacts, secreted factors and extracellular vesicles. According to secretome-wide profiling we identified plasminogen activator inhibitor -1 (PAI-1) to be the most prominent protein secreted by senescent ESCs (data are available via ProteomeXchange with identifier PXD015742). By applying CRISPR/Cas9 techniques we disclosed that PAI-1 secreted by senescent ESCs may serve as the master-regulator of paracrine senescence progression within the ESCs population. Unraveled molecular basis of senescence transduction in the ESCs population may be further considered in terms of altered endometrial plasticity and sensitivity to invading embryo, thus contributing to the female infertility curing.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular basis of senescence transmitting in the population of human endometrial stromal cells

Griukova

Deryabin

Shatrova

et al. 2019

Aging

View full text Add to dashboard Cite

show abstract

“…One example of this may be through NFκB activation of PAI-1. Multiple reports state that PAI-1 expression is significantly increased in the placenta of women with PE [74,75] and studies have shown PAI-1 can be induced via TNFα activation of NFκB, to decrease EVT invasion [63,64].…”

Section: Evt Function and Nfκb Actions In Preeclampsiamentioning

confidence: 99%

The Role of NFκB in Healthy and Preeclamptic Placenta: Trophoblasts in the Spotlight

Armistead

Kadam

Drewlo

et al. 2020

IJMS

View full text Add to dashboard Cite

The NFκB protein family regulates numerous pathways within the cell—including inflammation, hypoxia, angiogenesis and oxidative stress—all of which are implicated in placental development. The placenta is a critical organ that develops during pregnancy that primarily functions to supply and transport the nutrients required for fetal growth and development. Abnormal placental development can be observed in numerous disorders during pregnancy, including fetal growth restriction, miscarriage, and preeclampsia (PE). NFκB is highly expressed in the placentas of women with PE, however its contributions to the syndrome are not fully understood. In this review we discuss the molecular actions and related pathways of NFκB in the placenta and highlight areas of research that need attention

show abstract

“…Serpin Family E Member 1 ( SERPINE1 ), which is the inhibitor of tissue plasminogen activator and urokinase [107] that regulates fibrinolysis [108], appeared to be in the fifth place of the table. The SERPINE1 gene mediates the anti-apoptotic effect in the endothelial cell [109].…”

Section: Resultsmentioning

confidence: 99%

Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem

et al. 2019

View full text Add to dashboard Cite

BackgroundCurrently, more than 150 million people worldwide suffer from lymphedema. It is a chronic progressive disease characterized by high-protein edema of various parts of the body due to defects in lymphatic drainage. Molecular-genetic mechanisms of the disease are still poorly understood. Beginning of a clinical manifestation of primary lymphedema in middle age and the development of secondary lymphedema after treatment of breast cancer can be genetically determined. Disruption of endothelial cell apoptosis can be considered as one of the factors contributing to the development of lymphedema. However, a study of the relationship between genes associated with lymphedema and genes involved in endothelial apoptosis, in the associative gene network was not previously conducted.MethodsIn the current work, we used well-known methods (ToppGene and Endeavour), as well as methods previously developed by us, to prioritize genes involved in endothelial apoptosis and to find potential participants of molecular-genetic mechanisms of lymphedema among them. Original methods of prioritization took into account the overrepresented Gene Ontology biological processes, the centrality of vertices in the associative gene network, describing the interactions of endothelial apoptosis genes with genes associated with lymphedema, and the association of the analyzed genes with diseases that are comorbid to lymphedema.ResultsAn assessment of the quality of prioritization was performed using criteria, which involved an analysis of the enrichment of the top-most priority genes by genes, which are known to have simultaneous interactions with lymphedema and endothelial cell apoptosis, as well as by genes differentially expressed in murine model of lymphedema. In particular, among genes involved in endothelial apoptosis, KDR, TNF, TEK, BMPR2, SERPINE1, IL10, CD40LG, CCL2, FASLG and ABL1 had the highest priority. The identified priority genes can be considered as candidates for genotyping in the studies involving the search for associations with lymphedema.ConclusionsAnalysis of interactions of these genes in the associative gene network of lymphedema can improve understanding of mechanisms of interaction between endothelial apoptosis and lymphangiogenesis, and shed light on the role of disturbance of these processes in the development of edema, chronic inflammation and connective tissue transformation during the progression of the disease.Electronic supplementary materialThe online version of this article (10.1186/s12920-019-0492-9) contains supplementary material, which is available to authorized users.

show abstract

Role of Plasminogen Activator Inhibitor Type 1 in Pathologies of Female Reproductive Diseases

Cited by 78 publications

References 137 publications

Molecular basis of senescence transmitting in the population of human endometrial stromal cells

Molecular basis of senescence transmitting in the population of human endometrial stromal cells

The Role of NFκB in Healthy and Preeclamptic Placenta: Trophoblasts in the Spotlight

Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem

Contact Info

Product

Resources

About