Matrix metalloproteinase-9 increases and Interleukin-10 reduces with increase in body mass index in polycystic ovary syndrome: A cross-sectional study

Sylus, Angel Mercy; Nandeesha, Hanumanthappa; Thiagaraju, Chitra

doi:10.18502/ijrm.v13i8.7502

Cited by 4 publications

(3 citation statements)

References 33 publications

(34 reference statements)

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“…2 a). It is well documented that PCOS patients exhibit significantly lower serum levels of IL-10 compared to healthy counterparts [ 42 , 65 , 66 ]. This triggered us to focus on this important immune-suppressive cytokine.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10

et al. 2021

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Background Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models. Methods For in vitro experiment, we treated conditioned media from BM-hMSC to androgen-producing H293R cells and analyzed androgen-producing gene expression. For in vivo experiment, BM-hMSC were implanted into letrozole (LTZ)-induced PCOS mouse model. BM-hMSC effect in androgen-producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery. Results BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improved in metabolic and reproductive markers in our PCOS model and able to restore fertility. Conclusion Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10

et al. 2021

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“…Matrix metalloproteinase-9(MMP9) may play an essential role in PCOS and NAFLD.A study [30] proves that PCOS patients have elevated serum concentrations of MMP-2 and MMP-9.Another [31]proves that MMP9 may be involved in the pathogenesis of PCOS and matrix metalloproteinases (MMPs) play vital roles in follicular development.A recent study [32]makes a rat model of PCOS and proves that metformin treatment by decreasing the expression of MMP-2 and MMP-9 alleviates PCOS.Another [33]proves that MMP-9 levels are increased in obese PCOS women. Moreover,study [34]made a rodent model of non-alcoholic steatohepatitis present that MMP-9 activity is negatively correlates with adiponectin-which can protect from in ammation and brosis in metabolic liver disease.Besides,study [35]proves that MMP-9 de ciency enhances regeneration of steatotic livers.Study [36]proves that MMP9 levels can act as predictive factors for poor prognosis of nonalcoholic fatty liver patients .…”

Section: Discussionmentioning

confidence: 95%

Identification the key genes between polycystic ovary syndrome and Non-Alcoholic Fatty Liver Disease

2021

Preprint

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Purpose Many studies show correlation between polycystic ovary syndrome(PCOS) and non-alcoholic fatty liver disease(NAFLD),but the underlying pathogenic genes are not clear. This study by using the bioinformatics method aims to search the key genes involved in these 2 diseases. Methods The Gene Expression Omnibus (GEO) datasets coming from the GEO database GSE63067 -NAFLD patients and healthy controls, and GSE34526 -PCOS patients and normal controls, are downloaded. Differentially expressed genes (DEGs) of 2 diseases datasets and the common genes are obtained. After GO and KEGG enrichment analyses of common genes are performed. To find the key genes between NAFLD and PCOS, a protein–protein interaction (PPI) network is carried out. In addition, the diagnostic value of key genes in PCOS is analyzed. Results According to NAFLD and PCOS downloaded datasets,34 common genes,21 key genes,15 GO terms and 4 KEGG pathways are obtained. Further,based on the top 6 key genes,the corresponding area under the curve (AUC) by constructing ROC curves in the PCOS is 0.909 (95% CI, 0.775–1.000). Conclusions The study identify some key genes in the occurrence and progression between NAFLD and PCOS. In the future,to verify our results,it need experimental and clinical research.

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“…The MMP-9 has been linked with several disorders other than endometriosis such as ovarian carcinoma [14], breast cancer [15], lung cancer [16], endometrial cancer [17], cervical cancer [18], neurodegenerative/ neural diseases [19], hypertensive disorder [20], autoimmune disorder [21], Cardiovascular diseases [22], osteoporosis [23], Arthritis such as rheumatoid arthritis and focal brain ischemia, Pregnancyassociated malaria (Placental malaria), Poly Cystic Ovary Syndrome [24], Uterine fibroids [25]. Also, high levels of MMP-9 were seen in the Covid-19 patients with respiratory failure [26].…”

Section: Mmp-9 Role In Various Disordersmentioning

confidence: 99%

Identification of Fungal Bioactive Compounds Targeting MMP-9 for Endometriosis- An In silico Approach

Nabiya

Devi

Rajamiriyam

2021

JPRI

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Background: Endometriosis is a chronic inflammatory disease of the female reproductive system characterized by the presence of endometrial tissue outside the uterus that affects 5 to 10% of women of reproductive age, which is approximately 176 million women in the world. The women suffering from endometriosis have been reported to have high levels of matrix metalloproteinase (especially MMP-9) which regulates the inflammatory process. Thus, the aim of this study is to investigate the naturally available anti-inflammatory fungal compounds that can target the MMP-9 by various in silico approaches. Methodology: A wide variety of anti-inflammatory bioactive compounds were screened and five compounds were further selected based on ‘Lipinski’s rule of five’ using the PubChem database. The bioavailability, pharmacokinetics, ADMET properties and biological activity of these compounds were predicted computationally using databases such as SWISS-ADME, PubChem, pkCSM and PASS. The target 1L6J (Crystal structure of human matrix metalloproteinase MMP-9) structure was retrieved from the PDB database. Comparative analysis of the bioactive compounds with the target was performed by AutoDock 4.2.6 and further visualisation of the target residues interacting with the compounds was performed using LigPlot v.2. 2. tool. Results: Based on the docking results, the compounds namely, Ergosterol peroxide, Lovastatin, Javanicin, Asperlin and Ergothioneine exhibited binding energy value of -10.25 kcal/mol, -8.4 kcal/mol, -7.64 kcal/mol, -7.07 kcal/mol and -6.19 kcal/mol respectively whereas Elagolix (control drug) exhibited binding energy value of -4.88 kcal/mol, thus, indicating that the selected bioactive compounds were seen to have better binding energy comparative to the control drug. Conclusion: Ergosterol peroxide derived from edible mushroom might act as a potential lead compound for designing a therapeutic drug for treating endometriosis and this compound can further be explored to evaluate its level of toxicity and efficacy in the wet laboratory studies by in vitro and in vivo methods.

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Matrix metalloproteinase-9 increases and Interleukin-10 reduces with increase in body mass index in polycystic ovary syndrome: A cross-sectional study

Cited by 4 publications

References 33 publications

Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10

Mesenchymal stem cell therapy ameliorates metabolic dysfunction and restores fertility in a PCOS mouse model through interleukin-10

Identification the key genes between polycystic ovary syndrome and Non-Alcoholic Fatty Liver Disease

Identification of Fungal Bioactive Compounds Targeting MMP-9 for Endometriosis- An In silico Approach

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