scholarly journals Reduced Histone H3 Lysine 9 Methylation Contributes to the Pathogenesis of Latent Autoimmune Diabetes in Adults via Regulation of SUV39H2 and KDM4C

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Xi-yu Liu ◽  
Hong Li
Keyword(s):  
Autoimmune Disease ◽  
T Lymphocytes ◽  
Histone Methylation ◽  
Autoimmune Diabetes ◽  
Glycosylated Hemoglobin ◽  
Methylation Status ◽  
Histone H3 ◽  
Histone Demethylase ◽  
Healthy Controls ◽  
Latent Autoimmune Diabetes

Aims. Latent autoimmune diabetes in adults (LADA) is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity.Methods. Blood CD4+T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status.Results. Reduced global H3 lysine 9 methylation was observed in LADA patients’ CD4+T lymphocytes, compared to healthy controls (P< 0.05). H3 lysine 4 methylation was not statistically different. The reduced H3 lysine 9 methylation was associated with GADA titer but not correlated with glycosylated hemoglobin (HbA1c). When the LADA patient group was divided into those with complication and those without, relatively reduced global H3 lysine 9 methylation was observed in LADA patients with complication (P< 0.05). The expression of histone methyltransferase SUV39H2 for H3 lysine 9 methylation was downregulated in LADA patients, and the expression of histone demethylase KDM4C which made H3 lysine 9 demethylation was upregulated.Conclusion. The reduction of histone H3 lysine 9 methylation which may due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in CD4+T lymphocytes of LADA patients.

scholarly journals Reduced Histone H3 Acetylation in CD4+T Lymphocytes: Potential Mechanism of Latent Autoimmune Diabetes in Adults

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Xi-yu Liu ◽  
Jiang-feng Xu
Keyword(s):  
Gene Expression ◽  
T Lymphocytes ◽  
Histone Deacetylases ◽  
Autoimmune Diabetes ◽  
Histone H3 ◽  
Histone Acetyltransferases ◽  
Healthy Controls ◽  
Latent Autoimmune Diabetes ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

Aims. Latent autoimmune diabetes in adults (LADA) is the result of gene-environment interactions. Histone acetylation regulates gene expression and maybe interpret how environmental factors modify LADA. Hence, we studied the histone acetylation patterns in CD4+T lymphocytes from LADA patients.Methods. Blood CD4+T lymphocytes from 28 patients with LADA and 28 healthy controls were obtained to detect histone H3 acetylation and H4 acetylation. The gene expression of histone acetyltransferases (P300 and CREBBP) and histone deacetylases (HDAC1, HDAC2, and HDAC7) was measured by real-time polymerase chain reaction (RT-PCR).Results. Compared to healthy controls, reduced global H3 acetylation was observed in LADA patients’ CD4+T lymphocytes (P<0.05). Global level of H4 acetylation was not statistically different. Among LADA, CD4+T lymphocytes H3 acetylation was associated with glycosylated hemoglobin (HbA1c) and GADA titer. Compared to healthy controls, the expression of histone acetyltransferases CREBBP in LADA patients was downregulated, and the expression of histone deacetylases HDAC1 and HDAC7 was upregulated.Conclusion. A concerted downregulation of histone H3 acetylation was found in CD4+T lymphocytes of LADA patients, and this might provide evidence of a novel epigenetic explanation for the pathogenesis of LADA and its complications.

scholarly journals Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2

2021 ◽  
Vol 22 (20) ◽  
pp. 11085
Author(s):  
Ji-Hyun Kim ◽  
Arukumar Nagappan ◽  
Dae Young Jung ◽  
Nanjoo Suh ◽  
Myeong Ho Jung
Keyword(s):  
Liver Disease ◽  
Hepatic Steatosis ◽  
Histone Methylation ◽  
Functional Role ◽  
Histone H3 ◽  
Diacylglycerol Acyltransferase ◽  
Histone Demethylase ◽  
Nonalcoholic Fatty Liver ◽  
Intracellular Triglyceride

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. While the development of NAFLD is correlated with aberrant histone methylation, modifiers of histone methylation involved in this event remain poorly understood. Here, we studied the functional role of the histone demethylase KDM7A in the development of hepatic steatosis. KDM7A overexpression in AML12 cells upregulated diacylglycerol acyltransferase 2 (DGAT2) expression and resulted in increased intracellular triglyceride (TG) accumulation. Conversely, KDM7A knockdown reduced DGAT2 expression and TG accumulation, and significantly reversed free fatty acids-induced TG accumulation. Additionally, adenovirus-mediated overexpression of KDM7A in mice resulted in hepatic steatosis, which was accompanied by increased expression of hepatic DGAT2. Furthermore, KDM7A overexpression decreased the enrichment of di-methylation of histone H3 lysine 9 (H3K9me2) and H3 lysine 27 (H3K27me2) on the promoter of DGAT2. Taken together, these results indicate that KDM7A overexpression induces hepatic steatosis through upregulation of DGAT2 by erasing H3K9me2 and H3K27me2 on the promoter.

scholarly journals Incidence and Risk Factors of Hypogonadism in Male Patients With Latent Autoimmune Diabetes and Classic Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Meili Cai ◽  
Ran Cui ◽  
Peng Yang ◽  
Jingyang Gao ◽  
Xiaoyun Cheng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Uric Acid ◽  
Diabetes Management ◽  
Autoimmune Diabetes ◽  
Glycosylated Hemoglobin ◽  
Diabetic Patients ◽  
Latent Autoimmune Diabetes ◽  
Male Patients

ObjectivesThis study aimed to compare the prevalence of hypogonadism between male patients with latent autoimmune diabetes (LADA) and type 2 diabetes (T2DM) and investigate the risk factors for hypogonadism in these patients.MethodsThis cross-sectional study evaluated 367 male patients with LADA (n=73) and T2DM (n=294) who visited the endocrinology department of Shanghai Tenth People’s Hospital between January 2016 and October 2019 for diabetes management. Sex hormones, lipid profiles, sex hormone-binding globulin (SHBG), glycosylated hemoglobin A1c, beta-cell function, uric acid, and osteocalcin were determined in serum samples. Hypogonadism was defined as calculated free testosterone (cFT) less than 220 pmol/L along with the presence of symptoms (positive ADAM score).ResultsThe rate of hypogonadism in the LADA and T2DM group were 8.2, and 21.7%, respectively (p=0.017). After adjusting possible confounders, the rate of hypogonadism in the LADA group was comparable to those of the T2DM group. Univariate logistic regressions demonstrated that age, BMI, fasting C-peptide, triglycerides, total cholesterol and uric acid were associated with hypogonadism in men with diabetes, BMI, triglycerides and estradiol were independent risk for hypogonadism in men with diabetes.ConclusionThis is the first evidence to explore the rate of hypogonadism in male patients with latent autoimmune diabetes (LADA). In the population requiring admission to a large urban hospital in China, the rate of hypogonadism was comparable to those of the T2DM group after adjusting for possible confounders. BMI, triglycerides and estradiol were independently associated with the presence of HH in male diabetic patients.

scholarly journals Abnormal Neutrophil Transcriptional Signature May Predict Newly Diagnosed Latent Autoimmune Diabetes in Adults of South China

2020 ◽  
Vol 11 ◽  
Author(s):  
Yixuan Xing ◽  
Qiuqiu Lin ◽  
Yue Tong ◽  
Wenzhi Zhou ◽  
Juan Huang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
South China ◽  
Autoimmune Diabetes ◽  
Receptor Interaction ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Rna Seq ◽  
Latent Autoimmune Diabetes ◽  
Study Results ◽  
Age And Sex

ObjectiveLatent autoimmune diabetes in adults (LADA) is an autoimmune diabetes characterized by slowly progressive of β-cell function deterioration. Our previous finding demonstrated that neutrophil numbers and migration abilities display distinct levels in different types of diabetes, including LADA, whereas its pathological alterations in the development of LADA remain unknown. We aimed to investigate the changes in transcriptional levels of peripheral neutrophils in newly diagnosed LADA.MethodsPeripheral blood neutrophils were isolated from newly diagnosed LADA patients (n = 5) and age-and sex-matched healthy controls (n = 5). The Transcriptomic signature was determined by RNA sequencing (RNA-seq). Differentially expressed genes (DEG) were screened, followed by analyzing downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Real-time polymerase chain reaction (qPCR) was applied for validation in LADA patients (n = 9) and age-and sex-matched healthy controls (n = 18), including sequencing samples.ResultsCompared with controls, 4105 DEG were screened in LADA patients, including 2661 upregulated and 1444 downregulated DEG. In GO analysis, DEG are mainly involved in leukocyte degranulation, myeloid cell differentiation, and immune response-regulating signaling. The top enriched KEGG pathways included cytokine-cytokine receptor interaction, adhesion molecule signaling, nuclear factor-κB (NF-κB) signaling and Th17 cell differentiation. Consistent with RNA-seq results, SELL, ITGA4, ITGAM, NCF4, ARHGAP3, and CLDN15 are upregulated in neutrophils by qPCR.ConclusionThe present study results provided a profile of DEG in the newly diagnosed LADA of south China. Our study reveals an abnormality in neutrophil disposition at the transcriptional level in LADA. Several essential genes may be involved in of LADA’s pathological process, which may be useful to guide prediction for LADA and further investigation into the pathogenesis for this disease.

scholarly journals The emerging role of KDM5A in human cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guan-Jun Yang ◽  
Ming-Hui Zhu ◽  
Xin-Jiang Lu ◽  
Yan-Jun Liu ◽  
Jian-Fei Lu ◽  
...  
Keyword(s):  
Histone Methylation ◽  
Posttranslational Modification ◽  
Human Cancer ◽  
Histone H3 ◽  
Epigenetic Inheritance ◽  
Histone Demethylase ◽  
Genome Integrity ◽  
Methyl Groups ◽  
Lysine Specific Demethylase

AbstractHistone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.

168-LB: Latent Autoimmune Diabetes in Youth (15–29 Years Old): The Heavier End of an Autoimmune Disease Spectrum

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 168-LB
Author(s):  
JIN CHENG ◽  
XIAOHAN TANG ◽  
XIANG YAN ◽  
SHUOMING LUO ◽  
XIA LI ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diabetes ◽  
Latent Autoimmune Diabetes ◽  
Disease Spectrum ◽  
Diabetes In Youth

scholarly journals Immunogenetic characteristics of LADA

2011 ◽  
Vol 14 (1) ◽  
pp. 28-34 ◽  
Author(s):  
Tatiana Vasil'evna Nikonova ◽  
Pavel Vasil'evich Apanovich ◽  
Elena Vladimirovna Pekareva ◽  
Vera Anatol'evna Gorelysheva ◽  
Svetlana Mikhailovna Stepanova ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Immune Tolerance ◽  
Autoimmune Diabetes ◽  
Tyrosine Phosphatase ◽  
Foxp3 Expression ◽  
Clinical Feature ◽  
Functional Changes ◽  
Control Subjects ◽  
Latent Autoimmune Diabetes ◽  
Gradual Development

Latent autoimmune diabetes of adults (LADA) is a variant of autoimmune diabetes mellitus. Its clinical feature not typical for classical DM1 despitethe presence of positive autoantibodies is characterized by the low rate of autoimmune destruction that accounts for the late development of insulindependence. Similar to classical DM1, LADA is associated with the loss of immune tolerance to autoantibodies. However, the quantitative andfunctional activity of Treg as key regulators of the immune response and main agents of immune tolerance remain as poorly known as their relationshipwith characteristics of apoptosis.Aim. To elucidate qualitative and functional changes at the level of immunity regulation in patients with LADA of different duration and theirrelationships with characteristics of apoptosis, immunological and genetic markers. Materials and methods. The study included 64 patients (45 men and 19 women) with LADA and 56 control subjects. The methods included HLAgenotyping, detection of autoantibodies against GAD, insulin, tyrosine phosphatase, islet cell antigens, composition of CD3+, CD4+, CD38+, HLADR+, CD25+, CD+25+, CD95, CD95L lymphocyte subpopulations, FoxP3 and C-peptide expression, HbA1c levels. Results. FoxP3 expression at the onset of LADA was similar to that in control subjects while the relative amount of CD425+high T-lymphocytes increased.In contrast to DM1, FoxP3 expression began to decrease 6-12 months after the onset of LADA when the amount of CD425+high T-lymphocytes loweredto become normal with the progress of the disease. Within 1-5 years after the onset of LADA, FoxP3 expression became normal again but significantlyincreased when its duration exceeded 5 years. Expression of apoptosis markers (CD95 and CD95L) on lymphocytes and of their soluble forms in allLADA patients was comparable with control. Conclusion. We for the first time determined intensity of FoxP3 expression and the amount of CD425+high T-lymphocytes in patients with differentduration of LADA. FoxP3 expression varies periodically while functional deficit of Treg is delayed and appears to be compensated by a rise in theirnumber. Increased population of Treg within 6 months after the onset of LADA may reflect their regulatory role (suppression of autoimmunity)accounting for the gradual development of the disease.

Abstract #265 Clinical Characteristic of 31 Patients Diagnosed with Latent Autoimmune Diabetes in Adults (Lada) in a Multicentric Study in Mexico

2019 ◽  
Vol 25 ◽  
pp. 103
Author(s):  
Raquel Faradji ◽  
Carmen Castillo-Galindo ◽  
Natalia De la Garza-Hernandez ◽  
Sigfrido Miracle-Lopez ◽  
Claudia Ramirez-Renteria ◽  
...  
Keyword(s):  
Autoimmune Diabetes ◽  
Multicentric Study ◽  
Latent Autoimmune Diabetes ◽  
Clinical Characteristic
Sign in / Sign up

Export Citation Format

Share Document