{"title":"Interference of Bisphenol A on Cumulus Cells Development and Number of Retrieved Mature Oocytes in Unexpected Poor Ovarian Response Women: A Prospective Cohort Study.","authors":"Somayeh Aftabsavad, Zahra Noormohammadi, Ashraf Moini, Morteza Karimipoor","doi":"10.22074/cellj.2024.2020628.1488","DOIUrl":"https://doi.org/10.22074/cellj.2024.2020628.1488","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the relationship between follicular fluid Bisphenol A (BPA) concentrations with alterations in the expressions of <i>NOTCH1-3, CASPASE 3/7, HLA-G,</i> and <i>ICAM-1</i> genes and the number of retrieved mature oocytes (MII oocyte) in the cumulus cells of infertile poor ovarian response stimulates women.</p><p><strong>Materials and methods: </strong>In this prospective cohort study, 80 infertile unexpected poor ovarian response (POR) subjects were selected on the basis of subgroup 1a of the POSEIDON classification. They were divided into two groups: group 1 consisted of 40 women, each with a higher number of metaphase II (MII) oocytes (G1, 3-4 oocytes retrieved), while group 2 comprised of 40 women, each with a lower number of MII oocytes (G2, ≤2 oocytes retrieved). The expressions of the studied genes were evaluated by quantitative-real time polymerase chain reaction (PCR). The concentration of BPA in follicular fluid was measured with HPLC.</p><p><strong>Results: </strong>The expression levels of <i>NOTCH1-3, HLA-G</i>, and <i>ICAM-1</i> genes were significantly lower in G2 than G1 (P<0.05). Meanwhile, <i>CASPASE 3/7</i> expression levels were higher in unexpected POR patients in G2 compared to G1 (P<0.05). There was a significant direct correlation between the levels of <i>NOTCH1-3, HLA-G</i> and <i>ICAM-1</i> gene expressions and there was also a significant inverse correlation (P<0.05) between the levels of CASPASE 3/7, with the number of MII oocytes and embryo development between the two groups. The concentration of BPA in the follicular fluids of G2 was higher compared to G1 (P<0.05).</p><p><strong>Conclusion: </strong>A higher concentration of BPA was associated with a lower number of mature oocytes and oocyte quality in these patients. Also, alterations of <i>NOTCH1-3, CASPASE 3/7, HLA-G,</i> and <i>ICAM-1</i> transcript levels in unexpected POR women were associated with BPA concentration.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 4","pages":"267-275"},"PeriodicalIF":2.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Upregulation of Oxidative Phosphorylation Genes in Cumulus Cells of The Polycystic Ovary Syndrome Patients with or without Insulin Resistance.","authors":"Behnaz Motiee, Seyed Omid Reza Mousavi, Maryam Eslami, Poopak Eftekhari-Yazdi, Fatemeh Hassani, Masood Bazrgar","doi":"10.22074/cellj.2024.2006763.1357","DOIUrl":"https://doi.org/10.22074/cellj.2024.2006763.1357","url":null,"abstract":"<p><strong>Objective: </strong>The relationship between oxidative stress (OS), insulin resistance (IR), and polycystic ovary syndrome (PCOS) is an important medical issue in human reproduction. Some of the oxidative phosphorylation (OXPHOS) genes have been previously studied in granulosa and muscle cells of PCOS patients. Cumulus cells (CCs) remain close to the oocyte even after ovulation. This research has been designed to compare the expression of OXPHOS genes in CCs of PCOS, with or without insulin resistance.</p><p><strong>Materials and methods: </strong>In this experimental study, patients were included in PCOS insulin-resistant, PCOS insulinsensitive (IS), and control (fertile women with male infertility history) groups. The expression of <i>NCF2, TXNIP, UCP2, NDUFB6, ATP5H, COX7C, NDUFA3, SDHA,</i> and <i>SDHB</i> was studied by real-time polymerase chain reaction (PCR), and normalization was performed considering <i>HPRT1</i> and <i>CYC1</i> as reference genes. One-way ANOVA and Tukey test were used for data analysis.</p><p><strong>Results: </strong>The results showed that the expression of <i>NCF2, TXNIP, UCP2,</i> and <i>ATP5H</i> was significantly higher in the IR group than IS and control groups (P<0.01). <i>NDUFB6</i> showed the highest expression in the IS group, which was significantly different from other groups (P<0.01). The other genes of interest, except <i>COX7C</i>, were observed with the most transcriptional levels in the IS group, although there was no significant difference for those genes.</p><p><strong>Conclusion: </strong>Altered expression of genes involved in mitochondrial function compared to the control group in CCs of both IR and IS categories of the PCOS patients suggests that alteration in OXPHOS genes can contribute to the pathophysiology of PCOS.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 4","pages":"235-242"},"PeriodicalIF":2.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell JournalPub Date : 2024-05-07DOI: 10.22074/cellj.2024.2022353.1504
Mohammad Reza Abbasi, Javad Jamshidian, Zahra Basir, Mohammad Reza Tabandeh
{"title":"Betaine Attenuates The Expression of Vasoactive Mediators and Histological Alterations Associated with Ovarian Hyperstimulation Syndrome in Rats.","authors":"Mohammad Reza Abbasi, Javad Jamshidian, Zahra Basir, Mohammad Reza Tabandeh","doi":"10.22074/cellj.2024.2022353.1504","DOIUrl":"https://doi.org/10.22074/cellj.2024.2022353.1504","url":null,"abstract":"<p><strong>Objective: </strong>Ovarian hyperstimulation syndrome (OHSS) is one female reproductive disorder that can occur after administration of injectable hormonal drugs to stimulate ovulation. Betaine (BET) is an intracellular biomolecule with anti-inflammatory and tissue protective effects. There is no information about its effects in an experimental model of OHSS. The current study aims to investigate the possible effects of BET on abnormal expressions of vasoconstrictor proteins and ovarian histological changes in an experimental OHSS rat model.</p><p><strong>Materials and methods: </strong>In this experimental study, 30 adult female rats (two months old) were randomly divided into six groups (n=5 per group): i. Control, ii. OHSS [10 IU sc equine chorionic gonadotropin (eCG) for 4 days followed by 30 IU sc human chorionic gonadotropin (hCG) on the fifth day], iii. OHSS+BET (200 mg/kg/day, orally for seven days), iv. OHSS+Cabergoline (CAB, 100 mg/kg/day, orally for six days), v. BET, and vi. CAB. Expression levels of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and blood levels of oestradiol (E2) and progesterone (P4) were measured at the end of the experiment. The ovaries were studied for histomorphological changes.</p><p><strong>Results: </strong>Induction of OHSS altered tissue histology, including an increase in the number of corpora lutea and atretic follicles, and decreased the number of follicular reserves. In this group, we observed increased expressions of the VEGF and COX-2 proteins, and increased serum E2 and P4 levels. Administration of CAB and BET significantly attenuated all molecular and histological alterations observed in the OHSS animals.</p><p><strong>Conclusion: </strong>Our findings, for first time, indicate the beneficial effects of BET to reduce OHSS complications in patients by reducing the expressions of vasoactive proteins and improving changes to the ovarian tissues. The findings are similar to CAB and can be a new avenue for future research on BET.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 4","pages":"259-266"},"PeriodicalIF":2.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell JournalPub Date : 2024-03-01DOI: 10.22074/cellj.2024.2014048.1432
Shaghayegh Kiani, Marziyeh Tavalaee, Fatemeh Maghool, Nahid Jamali, Mohammad Hassan Emami, Mohammad Hossein Nasr-Esfahani
{"title":"Sperm Parameters and Chromatin Integrity in Men Suffering from Celiac Disease: Insights into Reproductive Health, Case-Control Study.","authors":"Shaghayegh Kiani, Marziyeh Tavalaee, Fatemeh Maghool, Nahid Jamali, Mohammad Hassan Emami, Mohammad Hossein Nasr-Esfahani","doi":"10.22074/cellj.2024.2014048.1432","DOIUrl":"https://doi.org/10.22074/cellj.2024.2014048.1432","url":null,"abstract":"<p><strong>Objective: </strong>Celiac disease is a common chronic inflammatory condition of the small intestine caused by permanent intolerance to gluten/gliadin. It has been demonstrated that oxidative stress is one of the mechanisms that is involved in gliadin toxicity, and there is a correlation between oxidative damage with this disease. Similarly, increased oxidative stress was repeatedly reported in infertile men which led to low-quality of sperm function. Therefore, we aimed to assess sperm parameters and chromatin status in men with Celiac disease.</p><p><strong>Materials and methods: </strong>In this case-control study, semen samples were collected from 11 fertile men without Celiac and 10 men with diagnostic Celiac disease. Basic semen analyses were performed according to the World Health Organization (WHO) 2010 protocol. The percentage of sperm with persistence histones, protamine deficiency, DNA fragmentation, malondialdehyde (MDA), and intracellular reactive oxygen species (ROS) were assessed using aniline blue, chromomycin A3, sperm chromatin structure assay, thiobarbituric acid reactive substances (TBARS) assay, and diacetyldichlorofluorescein staining, respectively.</p><p><strong>Results: </strong>Unlike the sperm parameters, which did not show significant differences between men with Celiac disease and fertile individuals, sperm chromatin maturation (persistence histones and protamine deficiency) and sperm DNA damage in men with Celiac disease were significantly higher compared to fertile individuals (P<0.05). In addition, the percentage of sperm viability in these individuals was significantly lower than that in the fertile individuals (P<0.05). We did not observe any significant differences in sperm lipid peroxidation and intracellular ROS levels between the two study groups (P>0.05).</p><p><strong>Conclusion: </strong>Celiac disease affects sperm chromatin maturation and DNA fragmentation, emphasizing its impact on reproductive health.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 3","pages":"202-208"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>In Vivo</i> Vascularization of Endothelial Cells Derived from Bone Marrow Mesenchymal Stem Cells in SCID Mouse Model.","authors":"Abdolamir Allameh, Maryam Jazayeri, Maryam Adelipour","doi":"10.22074/cellj.2024.711902","DOIUrl":"https://doi.org/10.22074/cellj.2024.711902","url":null,"abstract":"<p><p>In this article published in Cell J, Vol 18, No 2, Jul-Sep (Summer) 2016, on pages 179-188, the authors found that Figure 2A was the same as the one that has already been published and it was confusing. The following figure's legend is corrected in reference 9. The authors would like to apologies for any inconvenience caused.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 3","pages":"212"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell JournalPub Date : 2024-03-01DOI: 10.22074/cellj.2024.2012548.1415
Nasrin Moheghi, Payam Sasannezhad, Andrew John Walley
{"title":"No Association between Single-Nucleotide Polymorphisms of The <i>S1PR1</i> Gene or Interleukin-17 Levels with Fingolimod Response in A Small Group of Iranian Relapsing-Remitting Multiple Sclerosis Patients: A Case-Control Study.","authors":"Nasrin Moheghi, Payam Sasannezhad, Andrew John Walley","doi":"10.22074/cellj.2024.2012548.1415","DOIUrl":"https://doi.org/10.22074/cellj.2024.2012548.1415","url":null,"abstract":"<p><strong>Objective: </strong>Multiple sclerosis (MS) has a multi-factorial etiology involving genetic factors. Fingolimod (Gilenya ®, FTY720) modulates the G-protein-coupled sphingosine 1-phosphate (S1P) receptors, <i>S1PR1</i>, 2, 3, 4 and 5. Variation in the human S1PR1 coding sequence results in heterogeneity in the function of the receptor. Interleukin-17, producing CD4+ T cells, tends to be increased after treatment with Fingolimod. The aim of the study was to investigate singlenucleotide polymorphisms (SNPs) in the <i>S1PR1</i> gene or interleukin-17 (IL-17) levels in a small group of Iranian relapsing-remitting MS patients treated with Fingolimod.</p><p><strong>Materials and methods: </strong>In this case-control study, the genomic DNA of 94 MS patients treated with Fingolimod was extracted and Sanger sequencing was performed on polymerase chain reaction (PCR) products to detect variants in the S1PR1 gene. Quantification of IL-17 from the serum of the patients was performed using a commercially available enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Among 94 relapsing-remitting MS patients treated with Fingolimod, 69 (73.4%) were responders and 25 (26.6%) were non-responders. There were four novel and five common SNPs in the <i>S1PR1</i> gene and no significant association between SNP genotype and drug response was detected. In a subset of 34 patients, there was no significant difference in IL-17 serum concentrations before or after treatment and no association with S1PR1 polymorphisms was determined.</p><p><strong>Conclusion: </strong>This study is the first in Iran to investigate association between SNPs of the <i>S1PR1</i> gene or IL-17 levels with fingolimod response in a small group of Iranian relapsing remitting MS patients. There was no association with <i>S1PR1</i> gene SNPs or IL-17 levels before or after treatment.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 3","pages":"185-193"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell JournalPub Date : 2024-03-01DOI: 10.22074/cellj.2024.2015571.1446
Sam Zarbakhsh, Parisa Hayat
{"title":"Effects of Idebenone on Rat Schwann Cells with Toxicity Induced by Hydrogen Peroxide: Assessment of Molecular, Apoptosis, and Oxidative Stress Parameters.","authors":"Sam Zarbakhsh, Parisa Hayat","doi":"10.22074/cellj.2024.2015571.1446","DOIUrl":"https://doi.org/10.22074/cellj.2024.2015571.1446","url":null,"abstract":"<p><strong>Objective: </strong>Schwann cells are the main cells for myelination and regeneration of peripheral nerves. Idebenone is a synthetic antioxidant used to treat central nervous system diseases. The aim of the study is to determine whether idebenone can protect Schwann cells and increase cell activity under conditions of oxidative stress caused by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) <i>in vitro</i>.</p><p><strong>Materials and methods: </strong>In this experimental study, Schwann cells were pre-treated with various concentrations of idebenone and H<sub>2</sub>O<sub>2</sub>; after determining the appropriate doses, the cells were treated with 10 μM idebenone for 48 hours and 1000 μM H<sub>2</sub>O<sub>2</sub> for the last two hours. The malondialdehyde (MDA) level, and activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were assessed by ELISA. Cell viability was assessed by the MTT assay. Western blot analysis was conducted to determine the expressions of myelin protein zero (MPZ) and peripheral myelin protein 22 (PMP22), and expression ratio of the Bax/Bcl-2 proteins. The percentage of cell apoptosis was evaluated by annexin V staining using flow cytometry.</p><p><strong>Results: </strong>Schwann cells under oxidative stress conditions caused by H<sub>2</sub>O<sub>2</sub> and treated with idebenone had increased cell viability; increased SOD, CAT, and GPx activity; and increased expressions of the MPZ and PMP22 proteins. There was a decreased level of MDA, decreased expression ratio of Bax/Bcl-2 proteins, and a decrease in the percentage of apoptotic cells stained with Annexin V.</p><p><strong>Conclusion: </strong>The appropriate dose of idebenone may improve both survival and function of Schwann cells exposed to H<sub>2</sub>O<sub>2</sub> by reducing oxidative stress and apoptosis.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 3","pages":"194-201"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell JournalPub Date : 2024-03-01DOI: 10.22074/cellj.2024.2024274.1523
Bahareh Sadri, Massoud Vosough
{"title":"2023, A Landmark Year in Biomedical Research; A Turning Point in Medical History.","authors":"Bahareh Sadri, Massoud Vosough","doi":"10.22074/cellj.2024.2024274.1523","DOIUrl":"https://doi.org/10.22074/cellj.2024.2024274.1523","url":null,"abstract":"<p><p>The rapid development of knowledge on healthy nutrition, and hygiene practices, as well as the advent of antibiotics and vaccines, has led to increased life expectancy in the recent century. The extended lifespan has brought new challenges for healthcare professionals, including the management of chronic degenerative diseases, malignancies, and autoimmune disorders. Advanced therapeutic medicinal products (ATMPs) have emerged as a promising frontier alongside conventional therapeutic modalities, offering innovative solutions through cell-based therapies, gene therapy, and tissue engineering. Recent years have witnessed remarkable advancements in regenerative medicine and the launching of innovative ATMPs. Numerous ATMPs have been registered and approved by regulatory agencies for the management of different diseases in 2023. The approval of groundbreaking therapies around the world has made 2023 an exceptional year. Novel ATMPs and the development of artificial intelligence (AI) in 2023 will pave the way for the integration of ATMPs and advanced technologies in personalized medicine, early diagnosis and targeted treatments.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 3","pages":"210-211"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mesenchymal Stem Cells in Regenerative Medicine, Possible Applications in The Restoration of Spermatogenesis: A Review.","authors":"Dariush Irani, Davood Mehrabani, Feridoun Karimi-Busheri","doi":"10.22074/cellj.2024.2015141.1442","DOIUrl":"https://doi.org/10.22074/cellj.2024.2015141.1442","url":null,"abstract":"<p><p>Infertility is a common clinical condition and about half of the major causes are due to male-related infertility. Pathogenesis of this abnormality is generally undefined; so establishing a proper treatment option is relatively uncertain. In recent years, several evidences demonstrated that mesenchymal stem cells (MSCs) can be a hope for innovative and efficient treatment of male infertility. This study reviews possible applications of MSCs in the restoration of spermatogenesis in male infertility of both humans and animals to suggest new avenues for future clinical practices. Articles published in \"PubMed\" and \"Google Scholar\" from January 1, 2000, to August 1, 2023, were investigated by searching items of \"mesenchymal stem cells\", \"cell therapy\", \"cell transplantation\", and, \"regenerative medicine\" keywords, in addition to the \"urology\", \"andrology\", \"reproductive medicine\", \"male infertility\", \"azoospermia\", and \"spermatogenesis\". The results obtained from the transplantation of MSCs in the treatment of male infertility seemed encouraging and they revealed the safety and efficacy of these cells to recover spermatogenesis; eventhough further stem cell research is still required before recruiting clinical application of MSCs in the treatment of human male infertility. Undertaking more well-defined, standardized, and reproducible protocols and enrolling larger sample sizes during a longer follow-up period can benefit the relevance of MSC transplantation in the restoration of spermatogenesis and treatment of male infertility. It seems that developing and utilizing stem cell transplantations, exosomes, scaffold delivery systems, and three dimensional (3D) culture methods may open a new window to getting more benefits from cell therapy in the treatment of men infertility.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 3","pages":"169-184"},"PeriodicalIF":2.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Atorvastatin's Therapeutic Potential in Atherosclerosis: Inhibiting TGF-β-Induced Proteoglycan Glycosaminoglycan Chain Elongation through ROS-ERK1/2-Smad2L Signaling Pathway Modulation in Vascular Smooth Muscle Cells.","authors":"Hossein Ghaderi-Zefrehi, Ghorban Mohammadzadeh, Mojtaba Rashidi, Maryam Adelipour, Hossein Babaahmadi Rezaei","doi":"10.22074/cellj.2023.2010482.1397","DOIUrl":"10.22074/cellj.2023.2010482.1397","url":null,"abstract":"<p><strong>Objective: </strong>According to the response-to-retention hypothesis, the inception of atherosclerosis is attributed to the deposition and retention of lipoprotein in the arterial intima, facilitated by altered proteoglycans with hyperelongated glycosaminoglycan (GAG) chains. Recent studies have elucidated a signaling pathway whereby transforming growth factor-β (TGF-β) promotes the expression of genes linked to proteoglycan GAG chain elongation (<i>CHSY1</i> and <i>CHST11</i>) via reactive oxygen species (ROS) and the downstream phosphorylation of ERK1/2 and Smad2L. Atorvastatin is known to exhibit pleiotropic effects, including antioxidant and anti-inflammatory. The purpose of the present research was to ascertain the influence of atorvastatin on TGF-β-stimulated expression of <i>CHSY1</i> and <i>CHST11</i> and associated signaling pathways using an <i>in vitro</i> model.</p><p><strong>Materials and methods: </strong>In this experimental study, vascular smooth muscle cells (VSMCs) were pre-incubated with atorvastatin (0.1-10 μM) prior to being stimulated with TGF-β (2 ng/ml). The experiment aimed to evaluate the phosphorylation levels of Smad2C, Smad2L, ERK1/2, the NOX p47phox subunit, ROS production, and the mRNA expression of <i>CHST11</i> and <i>CHSY1</i>.</p><p><strong>Results: </strong>Our research results indicated that atorvastatin inhibited TGF-β-stimulated <i>CHSY1</i> and <i>CHST11</i> mRNA expression. Further experiments showed that atorvastatin diminished TGF-β-stimulated ROS production and weakened TGF-β-stimulated phosphorylation of p47phox, ERK1/2, and Smad2L; however, we observed no effect on the TGF-β- Smad2C pathway.</p><p><strong>Conclusion: </strong>These data suggest that atorvastatin demonstrates anti-atherogenic properties through the modulation of the ROS-ERK1/2-Smad2L signaling pathway. This provides valuable insight into the potential mechanisms by which atorvastatin exerts its pleiotropic effects against atherosclerosis.</p>","PeriodicalId":49224,"journal":{"name":"Cell Journal","volume":"26 2","pages":"158-166"},"PeriodicalIF":2.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}