ABSTRACT
Objective To explore the expression of junctophilin 2(JP2)and fibroblast growth factor 23(FGF23)in a rabbit model of atrial fibrillation mediated-cardiomyopathy(AMC).Methods Rabbit models of atrial fibrillation(AF)were developed through rapid atrial stimulation and then divided into three groups:control group(pacemak-ers implanted without pacing,n=6),AF group(pacing with ejection fraction decrease＜10％,n=5),and AMC group(pacing with ejection fraction decrease≥10％,n=6).Echocardiography was performed to detect left ventric-ular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)and left ventricular ejection fraction(LVEF).JP2 and FGF23 were detected by ELISA method.Western blot and RT-qPCR were conducted to detect protein and mRNA expression of JP2 and FGF23.Results Left atrial diameter,right atrial diameter and right ventricular diameter increased and LVEF decreased in the AMC group as compared with the control group.AMC group had lower LVEF and larger aorta and right ventricle diameter.Compared with the control group,the ex-pression of FGF23(P＜0.001)and JP2(P＜0.01)in left atrial cardiomyocytes was significantly increased in the AF group,while the expression of JP2 was decreased in the AMC group(P＜0.001).AMC group had lower expression of JP2 and FGF23 compared with AF group.Compared to the control group,plasma concentration of JP2 and FGF23 increased in the AF group and FGF23 plasma concentration increased in the AMC group.Plasma concentration of FGF23 and JP2 was lower in AMC group than that in AF group.Conclusions FGF23 expression increased and JP2 expression decreased as found in the rabbit AMC model.
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Objective:To analyze the correlations between the prognosis of patients with pancreatic cancer and macrophage infiltration, and to find the differential gene correlated with macrophage infiltration in patients with pancreatic cancer through bioinformatics.Methods:A total of 32 patients with pancreatic cancer admitted to the First Hospital of Lanzhou University from June 2015 to December 2018 were selected as the research objects, including 19 males and 13 females, with the age of (61.8±2.8) years. Cancer tissues, adjacent tissues, and related clinical data were collected. F4/80 (macrophage marker) immunohistochemical staining was performed on the samples. The survival time was followed up and its correlation with the above indexes was analyzed. The pancreatic cancer data from The Cancer Genome Atlas (TCGA) database was used for bioinformatics analysis.Results:The survival time of pancreatic cancer patients was negatively correlated with degree of macrophage infiltration in cancer tissues ( r=-0.522, P=0.002), but not with adjacent tissues ( r=0.168, P=0.358). The degree of macrophage infiltration in cancer tissue combined with preoperative serum carbohydrate antigen 19-9 (CA19-9), tumor TNM stage and vascular invasion can predict survival up to 47.4% of the survival time ( R2=0.474). TCGA database bioinformatic analysis showed that in pancreatic cancer there were 95 differentially expressed genes significantly correlated with M2 macrophage infiltration, among which JPH3 (positive correlation) and IL17REL (negative correlation) were the main genes. Conclusion:The degree of macrophage infiltration in cancer tissue can be used as a prognostic factor for patients with pancreatic cancer, and the combination with preoperative serum CA19-9, tumor TNM stage and vascular invasion is more accurate in predicting the prognosis. The related mechanism of M2 macrophage infiltration can be studied around the differential genes such as JPH3 and IL17REL.
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Objective This research is to explore the Junctophilin-2 ( JPH2 ) expression in persistent atrial fibrillation with mitral valve disease.Methods The left atrial tissue samples were taken from 34 patients with mitral valve disease who underwent cardiac surgery.16 patients were in sinus rhythm, 18 patients had persistent atrial fibrillation.Western blot tech-nique was used to test the JPH2 expression, and the RT-PCR method was used to test the JPH2 gene expression.Results The Westernblot results showed JPH2 expression down-regulated in persistent atrial fibrillation group (0.94 ±0.29 vs.1.53 ± 0.61,P0.05).Expression of miRNA-24 was significantly up-regulated in patients with persistent atrial fibrillation(4.49 ±4.30 vs.1.72 ±1.08, P<0.05).There was no significant difference in mean age, gender, ejection fraction and NYHA among the two groups.But the left atrial diameter was significant larger in patients with persistent atrial fibrillation compared to those in sinus rhythm(P=0.02).Conclusion Junctophilin-2 protein down-regulation may be associated with atrial fibrillation , cause left atrial remodeling and contraction dysfunction .
ABSTRACT
The normal cardiac function relies on highly specialized subcellular architectures. The subcellular domains junctional membrane complexes (JMCs) are essential for excitation-contraction coupling of the myocardium. Junctophilin-2 (JPH2) has been widely recognized as the crucial structural protein involved in JMCs. Initial studies limited the role of JPH2 to anchoring junctional sarcoplasmic reticulum (SR) and transverse-tubule (T-tubule) membrane invaginations. Recently, researchers have found an expanded role of JPH2 in the development of postnatal T-tubule in mammals, progression of disease in failing hearts, hypertrophic cardiomyopathy and arrhythmias. In this review we summarized the role of JPH2 in the above physiological or pathophysiological processes and discussed the perspective in future investigation.