scholarly journals Dysregulated levels of glycogen synthase kinase-3β (GSK-3β) and miR-135 in peripheral blood samples of cases with nephrotic syndrome

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10377
Author(s):  
Mohammadreza Ardalan ◽  
Seyyedeh Mina Hejazian ◽  
Hassan Fazlazar Sharabiyani ◽  
Farahnoosh Farnood ◽  
Amirhossein Ghafari Aghdam ◽  
...  

Background Glycogen synthase kinase-3 (GSK-3β) is a serine/threonine kinase with multifunctions in various physiological procedures. Aberrant level of GSK-3β in kidney cells has a harmful role in podocyte injury. Methods In this article, the expression levels of GSK-3β and one of its upstream regulators, miR-135a-5p, were measured in peripheral blood mononuclear cells (PBMCs) of cases with the most common types of nephrotic syndrome (NS); focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). In so doing, fifty-two cases along with twenty-four healthy controls were included based on the strict criteria. Results Levels of GSK-3β mRNA and miR-135 were measured with quantitative real-time PCR. There were statistically significant increases in GSK-3β expression level in NS (P = 0.001), MGN (P = 0.002), and FSGS (P = 0.015) groups compared to the control group. Dysregulated levels of miR-135a-5p in PBMCs was not significant between the studied groups. Moreover, a significant decrease was observed in the expression level of miR-135a-5p in the plasma of patients with NS (P = 0.020), MGN (P = 0.040), and FSGS (P = 0.046) compared to the control group. ROC curve analysis approved a diagnostic power of GSK-3β in discriminating patients from healthy controls (AUC: 0.72, P = 0.002) with high sensitivity and specificity. Conclusions Dysregulated levels of GSK-3β and its regulator miR-135a may participate in the pathogenesis of NS with different etiology. Therefore, more research is needed for understanding the relationship between them.

2019 ◽  
Vol 17 ◽  
pp. 205873921882022
Author(s):  
Ge Zhang ◽  
Wei Huang ◽  
Ying Wang

The study aimed to detect the expression level of interleukin-37 (IL-37) in patients with rheumatoid arthritis (RA) and explore its clinical significance. A total of 40 peripheral blood samples from active and stable RA patients were collected (40 patients with RA), and peripheral blood from 40 healthy volunteers was used as the control group. Peripheral blood serum and peripheral blood mononuclear cells (PBMCs) were isolated. The expression of IL-37 mRNA in PBMCs was detected by real-time fluorescence quantitative PCR. Serum levels of IL-37, rheumatoid factor (RF), and anticyclic citrullinated peptide antibody (CCP) were measured by enzyme-linked immunosorbent assay (ELISA). The results were then calculated and analyzed. The results showed that expression of IL-37 mRNA in the PBMCs of patients with RA was significantly higher than that in the control group ( P < 0.05). Expression of IL-37 mRNA in the PBMCs of the active period group was significantly higher than that in the stable period group ( P < 0.05). IL-37 levels in patients with RA were significantly higher than those of the control group ( P < 0.05). IL-37 levels in the active period group were also significantly higher than those of the stable period group ( P < 0.05). The comparative analysis of RF and anti-CCP antibody levels showed that IL-37 was positively correlated with RF and anti-CCP levels in patients with RA. In conclusion, the expression level of IL-37 in peripheral blood of RA patients was significantly higher than that of normal control group, and it was correlated with RF and CCP antibody levels, indicating that IL-37 plays an important role in the development of RA.


2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Wei Wu ◽  
Xingxing Liu ◽  
Longfei Han

Abstract To evaluate the role of glycogen synthase kinase-3β (GSK-3β) in the apoptosis of cardiomyocytes in diabetic cardiomyopathy (DCM). Diabetes mellitus (DM) in rats was induced by intraperitoneal injection of 1% streptozotocin (STZ), and lithium chloride (LiCl) was used to decrease the expression of GSK-3β. Hematoxylin/eosin (HE) staining and the terminal deoxyribonucleotide transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay was conducted to evaluate the pathological injury and apoptosis of cardiomyocytes respectively. Western blot was applied to detect the protein expressions of Cleaved-caspase 3, caspase 3, Bax and Bcl-2 in rat cardiomyocytes. Real-time polymerase chain reaction (RT-PCR) was applied to detect the gene expressions of phosphoinositide 3-kinases (PI3K), Akt, and GSK-3β in rat cardiomyocytes. DM-induced cardiomyocyte injuries, which were presented as capillary basement membrane thickening, interstitial fibrosis, cardiomyocyte hypertrophy and necrosis in HE staining and increased apoptosis detected by TUNEL assay. When comparing with the control group, the mRNA expression of PI3K and Akt in DM group obviously decreased but the mRNA expression of GSK-3β obviously elevated (P < 0.05). In addition, the ratio of Cleaved-caspase 3/caspase 3 and Bax/Bcl-2 were notably increased in DM group compared with control group (P < 0.05). LiCl, as an inhibitor of GSK-3 apparently reduced the expression of GSK-3β mRNA (P < 0.05) but not the PI3K and Akt comparing with the DM group. LiCl also attenuated the myocardial injury and apoptosis induced by DM. The myocardial injury induced by DM is associated with the up-regulation of GSK-3β. LiCl inhibited the expression of GSK-3β and myocardial apoptosis in diabetic myocardium.


2021 ◽  
Vol 12 (1) ◽  
pp. 669-675
Author(s):  
Vishal Kumar Vishwakarma ◽  
Tarique Mahmood Ansari ◽  
Prabhat Kumar Upadhyay ◽  
Ritesh Kumar Srivastav ◽  
Farogh Ahsan ◽  
...  

High risks of cardiovascular diseases in women are associated with low estrogen levels. Ischemic preconditioning (IPC) exhibits protection in the heart by Glycogen synthase kinase-3β (GSK-3β) phosphorylation that inhibits the mPTP opening, and this protective action of IPC is attenuated by estrogen deficiency. An experiment was performed on female Wistar rats with/without ovariectomy (OVX). Isolated rat heart was attached with perfusion assembly. Infract size, coronary flow, LDH, CKMB and histopathology were estimated. Sham control group decreased the LDH, CKMB and infract size in normal rat heart. The IPC mediated protection of heart was attenuated in OVX rat heart. Inhibition of GSK-3β is found to enhance the threshold of mPTP opening during reperfusion. The treatment with atractyloside stuck significantly the protection of heart of IPC in normal and OVX rat heart. These observations show that downregulation of GSK-3β through an impaired opening of mPTP during reperfusion and GSK-3β might be potential adjuvant to IPC against cardiac injury in OVX challenged rats.  


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seyedeh Zahra Hosseini Imani ◽  
Zohreh Hojati ◽  
Sheyda Khalilian ◽  
Fariba Dehghanian ◽  
Majid Kheirollahi ◽  
...  

AbstractMultiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.


2021 ◽  
Author(s):  
Yasemin Gider ◽  
Xhariga Jabbarli ◽  
Gamze Uyaroglu ◽  
Seref Bugra Tuncer ◽  
Demet Akdeniz Odemis ◽  
...  

Abstract Background The most common cancers detected in women are breast, thyroid, colorectal, uterine corpus, lung, and ovarian cancer. Ovarian cancer is responsible from more than 150.000 death annually worldwide. This cancer is detected in the late stage, and is characterised with poor prognosis, therefore most cases result with death. The fact that this cancer manifests itself in the late stage and is characterized by a poor prognosis, is caused death in the majority of cases. Therefore, the diagnosis and the treatment of the disease have to be improved for a better quality of life for patients. MicroRNAs are the noncoding RNAs in the length of 19–24 nucleotides which show suppressor effect on target genes. miRNAs are included in the pathology of various diseases including cancer. miRNAs being as the biomarker candidates in diagnosis, and their use in treatment as the inhibitors of the molecules mimicking the miRNA showed that they may be used as the new therapeutic target and agents. Methods We detected with our group in our prior study conducted with disconcordant ovarian cancer twins that many miRNA molecules were different in ovarian cancer compared with the molecules in healthy sibling. The expression level of miR-142-3p that was selected from the miRNAs detected in the previous study was compared, and investigated in a wider ovarian cancer group, and in healthy control group. miR-142-3p expression level was investigated using the real-time PCR method in the present study involving 147 patients, and 100 healthy control group. The differences in the expression levels of miR-142-3p detected in the peripheral blood lymphocytes of ovarian cancer patients, and healthy control were statisticaly evaluated. Results The expression level of miR-142-3p was detected to have increased 3.11 fold in ovarian cancer patients compared with the levels in healthy controls, and the difference was statistically significant (p:0.00). These results suggest that miR-142-3p that was found significantly increased in the peripheral blood samples of ovarian cancer patients compared with the healthy controls might be used as a sensitive, noninvasive biomarker in the early diagnosis, and treatment and follow up of ovarian cancer.


2021 ◽  
Author(s):  
Seyedeh Zahra Hosseini Imani ◽  
Zohreh Hojati ◽  
Fariba Dehghanian ◽  
Sheyda Khalilian ◽  
Majid Kheirollahi ◽  
...  

Abstract Background Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction in myelin-less areas. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Results Our results showed that the expression level of IL7R was decreased in MS patients versus healthy controls. Also IL7R expression was significantly down-regulated in the sporadic group as compared to other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls was also seen. Our results represented an increased expression level of RNF213 in the familial patients as compared to the control group. Diagnostic evaluation was performed by ROC curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and EDSS with our gene expression levels were also assessed. Conclusions Overall, decreased expression level of IL7R and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. The RNF213 should be evaluated further for its potential as a candidate biomarker of inflammatory activity in MS in a larger cohort.


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