The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis

Sikora, Justyna; Wróblewska-Czech, Agnieszka; Smycz‐Kubańska, Marta; Mielczarek‐Palacz, Aleksandra; Cygal, Anna; Witek, Andrzej; Kondera-Anasz, Zdzisława

doi:10.1007/s00404-018-4754-0

Cited by 22 publications

(15 citation statements)

References 31 publications

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“…The presence of complement component (C4) and complement activation products (C3c SC5b-9) in the PF and in the sera of EM women have been previously described (38). Significantly higher PF levels of C1q, MBL and C1-INH in women with EM compared to control group has also been reported (39).…”

Section: Discussionmentioning

confidence: 84%

Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation

Agostinis

Zorzet

Balduit

et al. 2020

Preprint

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The pathophysiology of endometriosis (EM) is an excellent example of immune dysfunction, reminiscent of tumor microenvironment as well. Here, we report that an interplay between C3 and mast cells (MCs) is involved in the pathogenesis of ectopic EM. C3 is at the epicenter of the regulatory feed forward loop, amplifying the inflammatory microenvironment, in which the MCs are protagonists. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse, into the peritoneum of the recipient mice. The wild type mice showed greater amount of cyst formation in the peritoneum compared to C3 knock-out mice. This study offers an opportunity for novel therapeutic intervention in EM, a difficult to treat gynecological condition.SummaryC3 produced by the endometriotic tissue is involved in the lesion development through mast cell activation

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Section: Discussionmentioning

confidence: 84%

Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation

Agostinis

Zorzet

Balduit

et al. 2020

Preprint

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“…Swati et al revealed that chronic inflammation in endometriosis is dominated by complement 7 . Sikora et al had proved that abnormal activation of the complement pathway occurred in EMS and resulted in the overexpression of C1Q, MBL, C1INH 36 . In our study, we found that the up-regulated expression of the central complement factor (C1S, C1QA, C1R, and C3) in EMS, indicating that the abnormal status of complement might be involved in the pathogenesis of EMS.…”

Section: Discussionmentioning

confidence: 99%

Multi‐omics analysis reveals the interaction between the complement system and the coagulation cascade in the development of endometriosis

Shen

Ren

et al. 2021

Sci Rep

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Endometriosis (EMS) is a disease that shows immune dysfunction and chronic inflammation characteristics, suggesting a role of complement system in its pathophysiology. To find out the hub genes and pathways involved in the pathogenesis of EMs, three raw microarray datasets were recruited from the Gene Expression Omnibus database (GEO). Then, a series of bioinformatics technologies including gene ontology (GO), Hallmark pathway enrichment, protein–protein interaction (PPI) network and gene co-expression correlation analysis were performed to identify hub genes. The hub genes were further verified by the Real-time quantitative polymerase chain reaction (RT-PCR) and Western Blot (WB). We identified 129 differentially expressed genes (DEGs) in EMs, of which 78 were up-regulated and 51 were down-regulated. Through GO functional enrichment analysis, we found that the DEGs are mainly enriched in cell adhesion, extracellular matrix remodeling, chemokine regulation, angiogenesis regulation, epithelial cell proliferation, et al. In Hallmark pathway enrichment analysis, coagulation pathway showed great significance and the terms in which included the central complement factors. Moreover, the genes were dominating in PPI network. Combined co-expression analysis with experimental verification, we found that the up-regulated expression of complement (C1S, C1QA, C1R, and C3) was positively related to tissue factor (TF) in EMs. In this study, we discovered the over expression complement and the positive correlation between complement and TF in EMs, which suggested that interaction of complement and coagulation system may play a role within the pathophysiology of EMS.

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“…We observed increased levels of C3a in the peritoneal fluid of EM patients ( 118 ); Kabut et al ( 119 ) have also reported increased levels of C3c, C4, and sC5b-9 in the peritoneal fluid and serum of EM patients in comparison with healthy women. A recent study reported significantly higher concentrations of C1q, MBL and C1-INH in the peritoneal fluids of EM women as compared to the control group ( 120 ). No difference in plasma C3a levels between women with and without EM was found ( 121 ).…”

Section: Complement In Endometriosis Peritoneal Fluidmentioning

confidence: 93%

Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target

et al. 2021

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Endometriosis (EM) is a chronic disease characterized by the presence and proliferation of functional endometrial glands and stroma outside the uterine cavity. Ovaries and pelvic peritoneum are the most common locations for endometrial ectopic tissue, followed by deep infiltrating EM sites. The cyclic and recurrent bleeding, the progressive fibrosis and the peritoneal adhesions of ectopic endometrial glands, may cause different symptoms depending on the origin involved. EM is a frequent clinical condition affecting around 10% of women of mainly reproductive age, as well as in post-menopausal women and adolescents, especially with uterine anomalies. The risk of developing EM depends on a complex interaction between genetic, immunological, hormonal, and environmental factors. It is largely considered to arise due to a dysfunction of immunological surveillance. In fact, women with EM exhibit altered functions of peritoneal macrophages, lymphocytes and natural killer cells, as well as levels of inflammatory mediators and growth factors in the peritoneal fluid. In EM patients, peritoneal macrophages are preponderant and highly active compared to healthy women. Peritoneal macrophages are able to regulate the events that determine the production of cytokines, prostaglandins, growth factors and complement components. Several studies have shown alteration in the regulation of the complement activation, leading to chronic inflammation characteristic of EM. Aberrant regulation/activation of the complement system has been observed in the peritoneal cavity of women affected by EM. Thus, complement inhibition may represent a new approach for the treatment of EM, given that a number of complement inhibitors are under pre-clinical and clinical development. Such an intervention may provide a broader therapeutic control of complement-mediated inflammatory damage in EM patients. This review will focus on our current understanding of the role of complement activation in EM and possible modalities available for complement-based therapy.

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The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis

Cited by 22 publications

References 31 publications

Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation

Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation

Multi‐omics analysis reveals the interaction between the complement system and the coagulation cascade in the development of endometriosis

Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target

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