|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | An EGLN1 mutation may regulate hypoxic response in cyanotic congenital heart disease through the PHD2/HIF-1A pathway显示文摘Cyanotic congenital heart disease(CCHD),a term describing the most severe congenital heart diseases are characterized by the anatomic malformation of a right to left shunt.Although the incidence of CCHD are far less than the that of congenital heart diseases(CHD),patients with CCHD always present severe clinical features such as hypoxia,dyspnea,and heart failure.Chronic hypoxia induces hypoxemia that significantly contributes to poor prognosis in CCHD.Current studies have demonstrated that the prolyl-4-hydroxylase2(PHD2,encoded by EGLN1)/hypoxia-inducible factor-1A(HIF-1A)pathway is a key regulator of hypoxic response.Thus,we aim to assess the associations of single polymorphisms(SNPs)of the EGLN1 gene and hypoxic response in CCHD.A missense variant of EGLN1 c.380G>C(rs1209790)was found in 46 patients(46/126),with lower hypoxia incidence and higher rate of collateral vessel formation,compared with the wild type(P<0.05).In vitro experiments,during hypoxia,EGLN1 mutation reduced EGLN1 expression compared with the wild type,with higher HIF-1A,VEGF and EPO expression levels in the mutant.No difference in HK1 expression was observed between the mutant and wild type.CCHD patients with c.380G>C showed improved response to hypoxia compared with the wild-type counterparts.The EGLN1 c.380G>C mutation improves hypoxic response through the PHD2/HIF-1A pathway,which may provide a molecular mechanism for hypoxic response in CCHD.The effects of the EGLN1 c.380G>C mutation on CCHD prognosis deserve further investigation. | Yuanlin Zhou Na Ouyang Lingjuan Liu Jie Tian Xupei Huang Tiewei Lu | 2019 | Genes & Diseases2019，6，1： | 7 |
| 2 | Acetylation of H3K4,H3K9,and H3K27 mediated by p300 regulates the expression of GATA4 in cardiocytes显示文摘GATA4 is a particularly important cardiogenic transcription factor and serves as a potent driver of cardiogenesis.Recent progress in the field has made it clear that histone acetylation can influence gene expression through changing the structure of chromatin.Our previous research had revealed that hypo-acetylation could repress gata4 expression in cardiocytes,however the underlying mechanism by which this occurred was still unclear.To reveal the mechanism of histone acetylation involved in the regulation of gata4 transcription,we concentrated on P300,one of the important histone acetyltransferase associated with cardiogenesis.We found that P300 participated in gata4 expression through regulating histone acetylation in embryonic mouse hearts.RNAi-mediated downregulation of P300 modulated the global acetylation of H3 and the acetylation of H3K4,H3K9,and H3K27 in gata4 and Tbx5 promoters.Interestingly,there was an obvious inhibition of gata4 transcription,whereas Tbx5 was not influenced.Furthermore,SGC-CBP30,the selective inhibitor of the bromodomain in CBP/P300,downregulated gata4 transcription by repressing the acetylation of H3K4,H3K9,and H3K27 in the gata4 promoters.Taken together,our results identified that acetylation of H3K4,H3K9,and H3K27 mediated by P300 plays an important role in regulation of gata4 expression in cardiogenesis. | Wei Zhou Dagui Jiang Jie Tian Lingjuan Liu Tiewei Lu Xupei Huang Huichao Sun | 2019 | Genes & Diseases2019，6，3： | 3 |
| 3 | An eIF3a gene mutation dysregulates myocardium growth with left ventricular noncompaction via the p-ERK1/2 pathway显示文摘Left ventricular noncompaction(LVNC)is a heterogeneous disorder with undlear genetic causes and an unknown mechanism.elF3a,an important member of the Eukaryotic translation initiation factor 3(elF3)family,is involved in multiple biological processes,indluding cell prolif eration and migration during myocardial development,suggesting it could play a role in LVNC development.To investigate the association between a novel variant(C.1145 A->G)in elF3a and LVNC,and explore potential mechanisms that could lead to the development of LVNC.A novel elF3a variant,C.1145 A->G,was identified by whole-exome sequencing in a familial pedigree with LVNC.Adenovirus vectors containing wild-type elF 3a and the mutated version were constructed and co-infected into H9C2 cells.Cell proliferation,apoptosis,cell migration,and differentiation,as well as phosphorylation of ERK1/2 were stud-ied and were measured by proliferation assays,flow cytometry,real-time PCR and Westem blot,respectively.The elF3a mutation inhibited the proliferation of H9C2 cells,induced apoptosis,promoted cell migration,and inhibited the dif ferentiation of human induced plurip-otent stem cell-derived cardiomyocytes(hiPSC-CMs).The effect of the elF3a mutation may be attributed to a decrease in expression of p-ERK1/2.A novel elF3a gene mutation disrupted the p-ERK1/2 pathway and caused decreased myocardium proliferation,differentiation,acceler-ated migration.This finding may provide some insight into the mechanism involved in LVNC development. | Mei Ge Xuehan Bai Aoyi Liu Lingjuan Liu Jie Tian Tiewei Lu | 2021 | Genes & Diseases2021，8，4： | 1 |
| 4 | Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes显示文摘In the past studies,it is shown that cardiac troponin I(cTnI,encoded by TNNI3),as a cytoplasmic protein,is an inhibitory subunit in troponin complex,and involves in cardiomyocyte diastolic regulation.Here,we assessed a novel role of cTnI as a nucleoprotein.Firstly,the nuclear translocation of cTnI was found in mouse,human fetuses and rat heart tissues.In addition,there were differences in percentage of intranuclear cTnI in different conditions.Based on weighted gene co-expression network analyses(WGCNA)and verification in cell experiments,a strong expression correlation was found between TNNI3 and Atp2a2,which encodes sarco-endoplasmic reticulum Ca2t ATPase isoform 2a(SERCA2a),and involves in ATP hydrolysis and Ca2t transient.TNNI3 gain and loss caused Atpa2a2 increase/decrease in a dosedependent manner both in mRNA and protein levels,in vivo and in vitro.By using ChIP-sequence we demonstrated specific binding DNA sequences of cTnI were enriched in ATP2a2 promoter239we889 region and the specific binding sequence motif of cTnI was analyzed by software as'CCAT',which has been reported to be required for YY1 binding to the promoter region of YY1-related genes.Moreover,it was further verified that pcDNA3.1()-TNNI3 could express cTnI proteins and increase the promoter activity of Atp2a2 through luciferase report assay.In the end,we evaluated beat frequencies,total ATP contents,Ca2t transients in TNNI3-siRNA myocardial cells.These findings indicated,for the first time,cTnI may regulate Atp2a2 in cardiomyocytes as a co-regulatory factor and participate in the regulation of intracellular Ca ions. | Qian Lu Bo Pan Haobo Bai Weian Zhao Lingjuan Liu Gu Li Ruimin Liu Tiewei Lv Xupei Huang Xi Li Jie Tian | 2022 | Genes & Diseases2022，9，6： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员