scholarly journals Immunomodulatory Effect of H. Pylori CagA Genotype and Gastric Hormones On Gastric Versus Inflammatory Cells Fas Gene Expression in Iraqi Patients with Gastroduodenal Disorders

2016 ◽  
Vol 4 (3) ◽  
pp. 364-373
Author(s):  
Ali Ibrahim Ali Al-Ezzy
Keyword(s):  
Gene Expression ◽  
Lamina Propria ◽  
Gastric Gland ◽  
Inflammatory Cells ◽  
Serum Samples ◽  
Pepsinogen I ◽  
Significant Difference ◽  
H Pylori ◽  
Demographic Distribution ◽  
Gastroduodenal Disorders

AIM: To evaluate the Immunomodulatory effects of CagA expression; pepsinogen I, II & gastrin-17 on PMNs and lymphocytes Fas expression in inflammatory and gastric cells; demographic distribution of Fas molecule in gastric tissue and inflammatory cells.METHODS: Gastroduodenal biopsies were taken from 80 patients for histopathology and H. pylori diagnosis. Serum samples were used for evaluation of pepsinogen I (PGI); (PGII); gastrin-17 (G-17).RESULTS: Significant difference (p < 0.001) in lymphocytes & PMNs Fas expression; epithelial & lamina propria Fas localization among H. pylori associated gastric disorders. No correlation between grade of lymphocytes & PMNs Fas expression in gastric epithelia; lamina propria and types of gastric disorder. Significant difference (p < 0.001) in total gastric Fas expression, epithelial Fas; lamina propria and gastric gland Fas expression according to CagA, PGI; PGII; PGI/PGII; Gastrin-17. Total gastric Fas expression has significant correlation with CagA, PGII levels. Gastric epithelial and gastric lamina propria Fas expression have significant correlation with CagA, PGI; PGII levels. Significant difference (p < 0.001) was found in lymphocytes & PMNs Fas expression; epithelial & lamina propria localization of lymphocytes & PMNs Fas expression according to CagA, PGI; PGII; PGI/PGII; Gastrin-17. Lymphocytes Fas expression have correlation with PGI, PGII, PGI/PGII. PMNs Fas expression have correlation with PGI, PGII.CONCLUSION: Fas gene expression and localization on gastric and inflammatory cells affected directly by H. pylori CagA and indirectly by gastric hormones. This contributes to progression of various gastric disorders according to severity of CagA induced gastric pathology and gastric hormones disturbance throughout the course of infection and disease.

scholarly journals Involvement of Myeloid Dendritic Cells in the Development of Gastric Secondary Lymphoid Follicles in Helicobacter pylori-Infected Neonatally Thymectomized BALB/c Mice

2003 ◽  
Vol 71 (4) ◽  
pp. 2153-2162 ◽  
Author(s):  
Toshiki Nishi ◽  
Kazuichi Okazaki ◽  
Kimio Kawasaki ◽  
Toshiro Fukui ◽  
Hiroyuki Tamaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Dendritic Cells ◽  
Epithelial Cells ◽  
Lamina Propria ◽  
Myeloid Dendritic Cells ◽  
Lymphoid Follicles ◽  
Inflammatory Protein ◽  
H Pylori ◽  
Antigen Presenting

ABSTRACT We previously described an animal model of Helicobacter pylori-induced follicular gastritis in neonatally thymectomized (nTx) mice. However, it is still not clear whether antigen-presenting dendritic cells (DCs) in the stomach have a role in the development of secondary follicles in H. pylori-infected nTx mice. We investigated the distribution of DC subsets using this model and examined their roles. To identify lymphoid and myeloid DCs, sections were stained with anti-CD11c (pan-DC marker) in combination with anti-CD8α (lymphoid DC marker) or anti-CD11b (myeloid DC marker) and were examined with a confocal microscope. Expression of macrophage inflammatory protein 3α (MIP-3α), which chemoattracts immature DCs, was analyzed by real-time PCR and immunohistochemistry. Follicular dendritic cells (FDCs) were stained with anti-SKY28 antibodies. In noninfected nTx mice, a few myeloid and lymphoid DCs were observed in the bottom portion of the lamina propria, whereas in H. pylori-infected nTx mice, there was an increased influx of myeloid DCs throughout the lamina propria. FDC staining was also observed in the stomachs of members of the infected group. MIP-3α gene expression was upregulated in the infected nTx group, and the immunohistochemistry analysis revealed MIP-3α-positive epithelial cells. These data suggest that H. pylori infection upregulates MIP-3α gene expression in gastric epithelial cells and induces an influx of myeloid DCs in the lamina propria of the gastric mucosa in nTx mice. Myeloid DCs and FDCs might contribute to the development of gastric secondary lymphoid follicles in H. pylori-infected nTx mice.

scholarly journals Investigation the levels of endotoxin and 8-OHdG in sera of patients with H.pyloripositive peptic ulcer

2021 ◽  
Author(s):  
Nihayet Bayraktar ◽  
İslim Guler ◽  
Ismail Koyuncu ◽  
Mehmet Bayraktar
Keyword(s):  
Peptic Ulcer ◽  
Public Health Problem ◽  
The Body ◽  
Serum Samples ◽  
Important Public Health Problem ◽  
Damage Level ◽  
Significant Difference ◽  
Infected Cells ◽  
Antigen Tests ◽  
H Pylori

Background and aim: Peptic ulcer is considered an important public health problem and generally associated with complicated conditions such as bleeding and perforation. The aim of this study is to reflect the rate of oxidative damage in the body among patients with H. pylori positive peptic ulcer by measuring serum 8-hydroxy-2p-deoxyguanosine (8-OHdG) and its association with the level of bacterial endotoxin. Methods Patients applied to Harran University Gastroenterology Outpatient Clinic with dyspeptic complaints were enrolled in this study. According to gastrointestinal endoscopy findings, 43 patients with H.pylori positive peptiv ulcer patients and 43 healthy volunteers were included in this study. H.pylori diagnosis was detemined by H.pylori urea breath and stool antigen tests. Serum 8-OHdG and endotoxins were measued by ELISA. Results A total of 43 patients with peptic ulcer (13 females 30 males), 43 healthy individuals (16 females 27 males) ages (18- 70) years in the study. In biopsies taken endoscopically; Hp severity was mild in 19 patients (43.9%), moderate in 21 patients (48.5%), and severe in 3 patients (7.6%). 8-OHdG which has the potential to mark DNA damage level in serum samples of patients with H.pylori positive peptic ulcer, was compared with the healthy and patient group. It was observed that there was a statistically significant difference (p <0.01). In addition, a weak correlation was found between OHdG and endotoxin. Conclusion: Reactive oxygen species (ROS) produced due to increased endotoxin as a result of H. pylıori infection can attack nucleic acid in infected cells resulting in an increased in serum 8-OHdG level. H.pylori and its endotoxin had a significant in peptic ulcer pathogensis.

scholarly journals Use of a Novel Enzyme Immunoassay Based on Detection of Circulating Antigen in Serum for Diagnosis of Helicobacter pylori Infection

2004 ◽  
Vol 11 (4) ◽  
pp. 775-779 ◽  
Author(s):  
Abdelfattah M. Attallah ◽  
Hisham Ismail ◽  
Gellan G. Ibrahim ◽  
Mohamed Abdel-Raouf ◽  
Ahmed M. El-Waseef ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Endoscopic Biopsy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Antigen ◽  
Serum Samples ◽  
Predictive Values ◽  
Biopsy Specimens ◽  
Significant Difference ◽  
Circulating Antigen ◽  
H Pylori

ABSTRACT Recently, noninvasive diagnostic tests for Helicobacter pylori infection have gained in significance. We have developed a sensitive and specific noninvasive immunoassay based on the detection of an H. pylori circulating antigen (HpCA) in sera from H. pylori-infected individuals. Monospecific antibody and Western blot analyses were used to demonstrate the presence of the target antigen in H. pylori cell lysate and serum samples. A novel enzyme-linked immunosorbent assay (ELISA) was developed for the detection of HpCA in serum. Endoscopic biopsy specimens from the gastric antra of 221 individuals (143 males and 78 females) with dyspeptic symptoms were evaluated for H. pylori infection, with culture used as a “gold standard” for diagnosis. The target H. pylori antigen was identified at 58 kDa. HpCA has been detected by ELISA with high degrees of sensitivity, specificity, and efficiency (>90%), and ELISA results show no significant difference (P > 0.05) from results of H. pylori culture of gastric biopsy specimens. The test's positive and negative predictive values were also high (95 and 86%, respectively). In conclusion, a sensitive and specific immunoassay was developed for the detection of HpCA in human serum. This test can be applied for noninvasive laboratory and field diagnoses of H. pylori infection.

scholarly journals The burden of Helicobacter pylori infection in England and Wales

2002 ◽  
Vol 128 (3) ◽  
pp. 411-417 ◽  
Author(s):  
A. J. VYSE ◽  
N. J. GAY ◽  
L. M. HESKETH ◽  
N. J. ANDREWS ◽  
B. MARSHALL ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
High Reactivity ◽  
Antimicrobial Treatment ◽  
Active Infection ◽  
Serum Samples ◽  
England And Wales ◽  
Significant Difference ◽  
Specific Igg ◽  
H Pylori ◽  
Serum Elisa

The prevalence of active infection with Helicobacter pylori in the general population of England and Wales was estimated using high reactivity for specific IgG in serum ELISA as a marker. A total of 10118 anonymized residues of serum samples collected in 1986 and 1996 from persons aged 1–84 years were used. Estimated prevalence of active infection varied by region and was highest in London. Prevalence was related to decade of birth and increased from 4·3% in those born during the 1980s to 30% in those born before 1940. An estimated total of 7·5 million people living in England and Wales have an active infection and analysis by decade of birth showed no significant difference between samples collected in 1986 and 1996. These data suggest H. pylori infection is becoming less common, is acquired at an early age and is unlikely to be resolved unless suitable antimicrobial treatment is sought.

scholarly journals Effects of the hydrophilic extract of Juniperus excelsa on renal function in male Wistar rats

2018 ◽  
Vol 8 (1) ◽  
pp. 34-37
Author(s):  
Sadrollah Mehrabi
Keyword(s):  
Renal Function ◽  
Wistar Rats ◽  
Urine Volume ◽  
Inflammatory Cells ◽  
Control Group ◽  
Renal Tubules ◽  
Serum Samples ◽  
Juniperus Excelsa ◽  
Significant Difference ◽  
Male Wistar Rats

Introduction: Ores plant (Juniperus excelsa) has been used for a long-time in the treatment of kidney disease. Objectives: The aim of this study was to investigate the effects of J. excelsa extract on renal function in male Wistar rats. Materials and Methods: In this study, 32 male Wistar rats were randomly assigned into four groups of eight rats. Distilled water was used for the healthy control group and the other three groups received doses of 10%, 25% and 50% of the extract for one month. Prior to the intervention and on the 15th and 30th days after intervention, 24-hour urine was collected for measurement of protein, creatinine, and urine volume. On the 30th day, the rats were anesthetized with ether and in addition to the urinary samples, serum samples were taken directly from their heart to check for creatinine, urea, sodium, and potassium. Additionally, both kidneys were removed and examined for histological changes. Results: There was a significant difference between the groups before and after intervention regarding creatinine clearance (P=0.008). The mean serum urea on the 15th and 30th days of study was respectively 93±37.33 and 86.47±71.07 mg/dL (P=0.001). In pathology examination, minimal infiltration of inflammatory cells in the interstitium and mild decrease in thickness of renal tubules was observed in 50% dose of the extract. Conclusion: This study showed that the greatest impact of J. excelsa on the renal function of the male Wistar rats was in doses of 50% of the extracts.

scholarly journals Anti-inflammatory effect of HGF responses to traumatic oral ulcers using an HGF-Tg mouse model

2020 ◽  
Author(s):  
Xinhong Wang ◽  
Liting Yan ◽  
Yinghua Tang ◽  
Xiaoxi He ◽  
gang luo
Keyword(s):  
Statistical Significance ◽  
Inflammatory Cells ◽  
Neutrophil Infiltration ◽  
T Test ◽  
Serum Samples ◽  
Oral Ulcers ◽  
Histological Score ◽  
Significant Difference ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Background: Hepatocyte growth factor (HGF) has been implicated in inhibiting diverse types of inflammation and promoting wound healing. In this study, we demonstrate the anti-inflammatory effect of HGF on traumatic ulcer of oral mucosa using HGF overexpression transgenic C57BL/6 (HGF-Tg) mice. In total, 29 C57BL/6 (WT) and 29 HGF-Tg mice were used in this study. Traumatic ulcer of left mucosa was performed by abrasion using a n 15 surgery knife. Ulcer tissues and serum samples were collected on 5 th day, histological score, expression of inflammatory cells and serum cytokines expression were measured and analyzed. Results: There existed statistical significant difference in connective Ly6G positive cells and NF-кB positive expression, HGF-Tg mice showed lower number of positive cells ( p =0.048, p =0.020 ). Eotaxin ( t -test, p =0.002), MIP-1gamma ( t -test, p =0.011), BLC ( t -test, p =0.03),Eotaxin-2 ( t -test, p =0.027), RANTES ( t -test, p =0.038), Lix ( t -test, p =0.04) and IL-3 ( t -test, p =0.047) had statistical significance higher expression in HGF-Tg mice. No significant difference of blood T cells ( p =0.998), Neutrophils ( p =0.331),Macrophages ( p =0.470) and CD4+/CD8+ ratio ( p =0.451) between HGF-Tg and WT group. Conclusions: We observed that HGF-Tg animals presented less Ly6G-positive neutrophil infiltration, higher levels of circulating cytokines and less NF- к B expression in connective tissue, with a positive effect on the healing of oral traumatic ulcers. Key words: HGF, oral ulcer, cytokine, inflammation

Abstract 13103: Nourin-dependent Mirna-106b : A Novel Early Inflammatory Diagnostic Biomarker for Cardiac Injury

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Salwa A Elgebaly ◽  
Robert H Christenson ◽  
Hossam Kandil ◽  
Nashwa Elkhazragy ◽  
Laila Rashed ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Cells ◽  
Inflammatory Marker ◽  
Invasive Coronary Angiography ◽  
Cardiac Injury ◽  
Serum Samples ◽  
Inflammatory Biomarker ◽  
Significant Difference ◽  
Mirna 106B ◽  
Early Diagnose

Introduction: Nourin is an inflammatory mediator rapidly released by ischemic myocardium “before” necrosis, and by necrotic cells . It stimulates leukocyte “ chemotaxis ” and “ activates ” leukocytes and vascular endothelial cells to release several “ cytokine storm ” mediators. Using Nourin amino acid sequence, Bioinformatics analysis indicated that Nourin is likely regulated by miRNA-106b ; an inflammatory-signaling pathway linked to myocardial ischemia. Hypothesis: As an "initial" inflammatory marker, the Nourin-dependent miR-106b can early diagnose ischemia-induced injury in UA patients when Troponin levels are below the decision limit, and in STEMI patients. The underlying regulatory mechanism involves lncR-CTB89H12.4 and mRNA-ANAPC11; associated with ischemia. Methods: Gene expression of lncR-CTB89H12.4 / miR-106b and mRNA-ANAPC11 were measured in serum samples from UA (n=30 - confirmed by invasive coronary angiography and negative Troponin) and STEMI (n=16) patients at presentation, and healthy volunteers (n=16). Results: Gene expression of miR-106b was up-regulated by 150-fold in UA compared to healthy, and by 4.6-fold in STEMI compared to UA (Fig. 1). Receiving Operator Characteristics (ROC) analysis revealed a statistically significant difference in miR-106b that discriminated UA from healthy controls with a test sensitivity of 87% sensitivity & specificity of 88%. Diagnostic sensitivity was 86% and specificity was 90% for discriminating UA from STEMI. Additionally, Spearman’s correlation analysis revealed a significant association of miR-106b with lncR-CTB89H12.4 and mRNA-ANAPC11. The down regulation of lncR-CTB89H12.4 after ischemia resulted in the up-regulation of miR-106b and activation of mRNA-ANAPC11 . Conclusions: The Nourin-dependent miR-106b is a promising early inflammatory biomarker indicating UA patients and discriminating between UA and STEMI. Regulations appears to be from lncR-CTB89H12.4 and mRNA-ANAPC11 .

scholarly journals Immunopathological and Modulatory Effects of Cag A+ Genotype on Gastric Mucosa, Inflammatory Response, Pepsinogens, and Gastrin-17 Secretion in Iraqi Patients infected with H. pylori

2018 ◽  
Vol 6 (5) ◽  
pp. 794-802 ◽  
Author(s):  
Ali Ibrahim Ali AL-Ezzy
Keyword(s):  
Gene Expression ◽  
Duodenal Ulcer ◽  
Gastric Mucosa ◽  
P Value ◽  
Gastric Tissue ◽  
Igg Antibodies ◽  
Significant Difference ◽  
Specific Igg ◽  
H Pylori ◽  
Cag A

OBJECTIVE: To determine the immunopathological correlation between Cag A+ H. pylori-specific IgG; pepsinogen I&II (PI&PII); gastrin-17 (G-17); status of gastric and duodenal mucosa and inflammatory activities on different gastroduodenal disorders.METHODOLOGY: Eighty gastroduodenal biopsies were taken from patients with gastroduodenal disorders for histopathological evaluation and H. pylori diagnosis. Serum samples were used for evaluation of gastric hormones and detection of H. pylori-specific IgG antibodies. The tissue expression of H. pylori Cag A gene was detected by in situ hybridisation.RESULTS: H. pylori IgG antibodies were detected in (88.8%) of enrolled patients. According to Cag A gene expression, Significant difference (P value ˂ 0.05) was detected in levels of PG I; PGII, PG I/PG II among patients with gastric disorders. Serum G-17 level was negatively correlated with Cag A gene expression (P-value = 0.04). There was a significant correlation between H. pylori IgG and PG I; PG II; G-17. The current study revealed that corpus atrophic gastritis was diagnosed histologically with (5%) gastric ulcer cases; (3.75%) of duodenal ulcer cases; (3.75%) of duodenitis cases; (1.25%) of gastropathy cases and (8.75%) of gastritis cases. At the same time H. pylori gastritis diagnosed concurrently with (8.75%) of gastric ulcer cases; (11.25%) of duodenal ulcer cases; (17.5%) of gastropathy cases; (3.75%) of duodenitis cases and (2.5%) of prepyloric ulcer cases. A significant correlation was reported between the Immunopathological status of gastric mucosa and endoscopic mucosal finding among duodenal ulcer cases and gastritis cases only. A positive correlation was reported between serum levels of PGI; PGII; PGI/PGII; G-17; PMNs grade and Immunopathological status of the gastroduodenal mucosa of H. pylori Infected patients. A significant difference was reported in lymphocyte grades among gastric disorders without correlation with immunohistopathological changes in the mucosa (P-value = 0.002). A significant difference was reported in lymphocyte grades among different disorders according to H. pylori IgG. A significant difference was reported in serum level of PG I; PG II; PG I/PG II; G-17 according to PMN and lymphocyte grades (P-value ˂ 0.01). PMNs grades positively correlated with gastric Cag A expression; H. pylori IgG; PG II; G-17 levels. PG I; PG I/ PG II correlated with lymphocyte grades (P-value ˂ 0.05); while PGII has a negative correlation (P-value = 0.039).CONCLUSION: Endoscopic mucosal finding does not reflect exactly the actual immunopathological changes of gastric mucosa during H. pylori infection. Secretion of gastrin was not affected by the presence of Cag A in gastric tissue. Instead, the fluctuation in the hormone level appears to be due to the presence of H. pylori infection in gastric tissue. Gastric tissue infiltration with PMNs & lymphocytes inflammatory infiltrates has a direct effect on PGs and gastrin levels in serum of infected patients. The level of PG I; PG II; G-17 secretion correlated with the development of immune response against H. pylori and production of specific H. pylori IgG. Finally, H. pylori can modulate gastric secretions through Cag A dependent and independent pathways.

Linkage between H. pylori Infection and TNF-α polymorphism in The Pregnant Women

2018 ◽  
Vol 9 (SPL1) ◽  
Author(s):  
Ghaidaa Raheem Lateef ◽  
Azhar Omaran Al-Thahab
Keyword(s):  
Pregnant Women ◽  
Serum Antibody ◽  
Rapid Test ◽  
Negative Group ◽  
Positive Group ◽  
Gynecology And Obstetrics ◽  
Tnf Α ◽  
Significant Difference ◽  
Pcr Products ◽  
H Pylori

A study was performed on 100 pregnant women in the outpatient department of gynecology and obstetrics of Maternity and Children Hospital in Al-Diwaniya City during the period between (March to September 2016). One hundred blood samples (50 for patients and 50 for control) were collected under the supervision of the treating gynecologist. The detection of Helicobacter. pylori was done by the use of the serum antibody Rapid test. The results showed that 50 (100%) were positive and 50 (100%) were negative for H. pylori in above method.All blood of patients and control samples were used for the extraction of genomic DNA,where the 107 bp PCR product size. Genotyping of the TNF-α-308 SNP (G/A)was performed by restriction fragment length polymorphism PCR (RFLP-PCR). PCR products were digested with restr NcoI iction enzyme. Individuals with the TNF-α-308(GG) homozygote produced digested DNA bands at 80,and 20 bp bp. A heterozygous genotype ofTNF-α-308 (GA)produced 107 bp,80 bp,and 20 bp bands. Individuals with the TNF-α-308 (AA) homozygote genotype had no amplicon digested and generated only one band of 107 bp. There was a significant difference in the frequency of the TNF-α-308(GG)genotype between H. pylori positive group and H. pylori negative group(72%,78% respectively). Also for GA genotype,there was a significant difference between H. pylori positive group and H. pylori negative group(24%,18% respectively). Concerning the frequency of the TNF-α-308 (AA)genotype between H. pylori positive group and H. pylori negative group,there was no significant difference between the two groups.

ATF4, DLX3, FRA1, MSX2, C/EBP-ζ, and C/EBP-α Shape the Molecular Basis of Therapeutic Effects of Zoledronic Acid in Bone Disorders

2020 ◽  
Vol 20 (18) ◽  
pp. 2274-2284
Author(s):  
Faroogh Marofi ◽  
Jalal Choupani ◽  
Saeed Solali ◽  
Ghasem Vahedi ◽  
Ali Hassanzadeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zoledronic Acid ◽  
Mrna Expression ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Target Genes ◽  
Osteoblastic Differentiation ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Scheduled Time

Objective: Zoledronic Acid (ZA) is one of the common treatment choices used in various boneassociated conditions. Also, many studies have investigated the effect of ZA on Osteoblastic-Differentiation (OSD) of Mesenchymal Stem Cells (MSCs), but its clear molecular mechanism(s) has remained to be understood. It seems that the methylation of the promoter region of key genes might be an important factor involved in the regulation of genes responsible for OSD. The present study aimed to evaluate the changes in the mRNA expression and promoter methylation of central Transcription Factors (TFs) during OSD of MSCs under treatment with ZA. Materials and Methods: MSCs were induced to be differentiated into the osteoblastic cell lineage using routine protocols. MSCs received ZA during OSD and then the methylation and mRNA expression levels of target genes were measured by Methylation Specific-quantitative Polymerase Chain Reaction (MS-qPCR) and real.time PCR, respectively. The osteoblastic differentiation was confirmed by Alizarin Red Staining and the related markers to this stage. Results: Gene expression and promoter methylation level for DLX3, FRA1, ATF4, MSX2, C/EBPζ, and C/EBPa were up or down-regulated in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21. ATF4, DLX3, and FRA1 genes were significantly up-regulated during the OSD processes, while the result for MSX2, C/EBPζ, and C/EBPa was reverse. On the other hand, ATF4 and DLX3 methylation levels gradually reduced in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21, while the pattern was increasing for MSX2 and C/EBPa. The methylation pattern of C/EBPζ was upward in untreated groups while it had a downward pattern in ZA-treated groups at the same scheduled time. The result for FRA1 was not significant in both groups at the same scheduled time (days 0-21). Conclusion: The results indicated that promoter-hypomethylation of ATF4, DLX3, and FRA1 genes might be one of the mechanism(s) controlling their gene expression. Moreover, we found that promoter-hypermethylation led to the down-regulation of MSX2, C/EBP-ζ and C/EBP-α. The results implicate that ATF4, DLX3 and FRA1 may act as inducers of OSD while MSX2, C/EBP-ζ and C/EBP-α could act as the inhibitor ones. We also determined that promoter-methylation is an important process in the regulation of OSD. However, yet there was no significant difference in the promoter-methylation level of selected TFs in ZA-treated and control cells, a methylation- independent pathway might be involved in the regulation of target genes during OSD of MSCs.

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