Expression of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Endometriosis Menstrual Blood

Madjid, Tita Husnitawati; Ardiansyah, Dennis Fachmi; Permadi, Wiryawan; Hernowo, Bethy S.

doi:10.3390/diagnostics10060364

Cited by 11 publications

(11 citation statements)

References 18 publications

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“…Angiogenesis has an essential role in the establishment and growth of endometriotic lesions, regardless apoptosis [42,43]. Based on previous studies, it is shown that patients with endometriosis have much more active types of MMP-9 epithelial cells and menstrual stroma than those without endometriosis [44]. Our results in consistent with the findings of the above study confirmed the increase in migration genes (MMP2 and MMP9) of E-MenSCs compared to NE-MenSCs.…”

Section: Enhanced Migratory and Angiogenicsupporting

confidence: 92%

A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women

Sahraei

Asl

Kalhor

et al. 2022

BioMed Research International

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Background. Research into the pathogenesis of endometriosis would substantially promote its effective treatment and early diagnosis. Currently, accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. Objectives. We aimed to identify the differences in some genes’ expression between menstrual blood-derived mesenchymal stem cells (MenSCs) isolated from endometriosis patients (E-MenSCs) and MenSCs from healthy women (NE-MenSCs). Methods. Menstrual blood samples (2-3 mL) from healthy and endometriosis women in the age range of 22–35 years were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation method were characterized by flow cytometry. MenSCs were evaluated for key related endometriosis genes by real-time-PCR. Results. E-MenSCs were morphologically different from NE-MenSCs and showed, respectively, higher and lower expression of CD10 and CD9. Furthermore, E-MenSCs had higher expression of Cyclin D1 (a cell cycle-related gene) and MMP-2 and MMP-9 (migration- and invasion-related genes) genes compared with NE-MenSCs. Despite higher cell proliferation in E-MenSCs, the BAX/BCL-2 ratio was significantly lower in E-MenSCs compared to NE-MenSCs. Also, the level of inflammatory genes such as IL1β, IL6, IL8, and NF-κB and stemness genes including SOX2 and SALL4 was increased in E-MenSCs compared with NE-MenSCs. Further, VEGF, as a potent angiogenic factor, showed a significant increase in E-MenSCs rather than NE-MenSCs. However, NE-MenSCs showed increased ER-α and β-catenin when compared with E-MenSCs. Conclusion. Here, we showed that there are gene expression differences between E-MenSCs and NE-MenSCs. These findings propose that MenSCs could play key role in the pathogenesis of endometriosis and further support the menstrual blood retrograde theory of endometriosis formation. This could be of great importance in exploiting promising therapeutic targets and new biomarkers for endometriosis treatment and prognosis.

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Section: Enhanced Migratory and Angiogenicsupporting

confidence: 92%

A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women

Sahraei

Asl

Kalhor

et al. 2022

BioMed Research International

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“…Similarly, Shi and coworkers observed that the activities of MMP9 decreased in response to miR-126-5p agomir in a model of aortic smooth muscle cells transition ( 14 ). MiR-126 and MMP9 have been also suggested to play a role in development of endometriosis and MMP9 in particular, seems to be a potential marker of the disease ( 15 – 17 ). It has been also proposed that miR-126 acts as a tumor suppressor inhibiting proliferation, migration, and invasion by suppressing MMP2 and MMP9 expression and inactivating JAK2/STAT3 signaling pathway through targeting the EMT transcription factor ZEB1 ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Involvement of MIR-126 and MMP9 in the Pathogenesis of Intra-Abdominal Fistulizing Crohn’s Disease: A Brief Research Report

et al. 2022

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BackgroundIntra-abdominal fistulas are complications that affect a significant proportion of Crohn’s disease patients, often requiring surgery. The aim of the present work was to correlate the occurrence of intestinal fistulization to the clinico-pathological features of these patients and to the plasma levels of MMP9, a gelatinase involved in the pathophysiology of fistula formation, and of miR-126, appearing to modulate MMP9 expression.MethodsIn a series of 31 consecutive Crohn’s patients admitted to surgery due to therapeutic failure and/or complicated disease, we identified nine cases of abdominal fistulas, mainly entero-enteric fistulas. MMP9 protein was determined in plasma and at the intestinal level using immunometric assays. Circulating miR-126 was also measured in all plasma samples by real-time PCR.ResultsComparing patients with and without intra-abdominal fistulas, we did not observe differences in terms of age, gender, disease location and duration, number of previous surgeries and pre-biologic medications. However, cases with intra-abdominal fistulas had a significantly higher CDAI (p < 0.0001) and a significantly lower circulating miR-126 (p < 0.05). Patients with intra-abdominal fistulas had also a significantly higher amount of circulating MMP9 (p < 0.0001) and this data was correlated with an increased expression of MMP9 protein in the mucosa and with reduced levels of circulating miR-126. Receiver operating characteristic (ROC) analysis pointed out the ability of circulating MMP9 to discriminate patients with and without intra-abdominal fistulas.ConclusionsThese data confirm that circulating MMP9 can be used for the identification of cases with intra-abdominal fistulas and suggest that miR-126 may be also involved in the pathogenesis of this complication and that it may be further investigated as a new therapeutic strategy or for monitoring therapeutic response in these patients.

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“…The expression level of MMP-9 and TIMP-1 in the menstrual blood of endometriosis patients is related to the presence of endometriosis. (18) The imbalance between MMP-9 and TIMP-1 enhance the ectopic endometrium capability to invade and breakdown extracelullar matrix component in the process of implantation and development of endometriosis lesions. (15) However, the study about the correlation between MMP-9 activity and TIMP-1 expression with the invasion potential of endometrioma during the initial development of endometriosis has not been well explained.…”

Section: Introductionmentioning

confidence: 99%

MMP-9 and TIMP-1 Promote Extracellular Matrix Remodeling in the Formation of Ovarian Endometrioma: in vitro Study on Chicken Chorioallantoic Membrane

Sari¹,

Jenie²,

Widad³

et al. 2023

Indones Biomed J

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BACKGROUND: The invasion of endometrial tissue in the peritoneal layers is an important precursor to the formation of endometriosis. However, the mechanisms of the initial development of endometrioma remain unclear. This study aimed to explore the correlation between matrix metalloproteinase (MMP)-9 activity and tissue inhibitors of metalloproteinase (TIMP)-1 expression in the initial development of endometriosis through the invasion process of endometrial lesions in extracellular matrix (ECM) remodeling.METHODS: A total of 30 samples of endometrioma tissue were obtained from 24 women with endometriosis and examined at Dr. Sardjito General Hospital, Yogyakarta, Indonesia. The tissue was then implanted into a chicken chorioallantoic membrane (CAM) for five days to examine its invasion ability. The invasion scores were assessed using hematoxylin-eosin staining. MMP-9 activity and TIMP-1 expression were analyzed using gelatin zymography and western blot, respectively. The correlations between MMP-9 activity and TIMP-1 expressions with the invasion scores were analyzed using Spearman correlation tests with significance set as p<0.05.RESULTS: The results showed that there was a strong positive correlation between MMP-9 activity and invasion scores of endometriomas tissue (r=0.656; p=0.000). Meanwhile, expression levels of TIMP-1 had a weak negative correlation with the increase of invasion scores of endometrioma (r=-0.388; p=0.034). These results indicate the involvement of MMP-9 and TIMP-1 in the initial development of endometriosis during the ECM remodeling.CONCLUSION: MMP-9 activity and TIMP-1 expression were correlated with the invasion score of endometrioma tissue. This study provides evidence for understanding the mechanisms involved in ECM remodeling in the early process of endometriosis.KEYWORDS: endometrioma, extracellular matrix remodeling, MMP-9, TIMP-1

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Expression of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Endometriosis Menstrual Blood

Cited by 11 publications

References 18 publications

A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women

A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women

Involvement of MIR-126 and MMP9 in the Pathogenesis of Intra-Abdominal Fistulizing Crohn’s Disease: A Brief Research Report

MMP-9 and TIMP-1 Promote Extracellular Matrix Remodeling in the Formation of Ovarian Endometrioma: in vitro Study on Chicken Chorioallantoic Membrane

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