Similar Datasets
Project description:The activation of fibroblasts and production of extracellular matrix (ECM) after cardiac injury has been the focus of research on cardiac fibrosis. Whether imprinted genes play a role in the fibrogenesis or extracellular matrix production after heart damage has not been studied. Here, we show that the imprinted gene Pw1 directed ECM production by regulating de novo purine synthesis (DNPB) after myocardial infarction (MI). After MI, the DNA methylation of the imprinting control region (ICR) of Pw1 gene in the injured area was reduced and both alleles of Pw1 in fibroblasts are activated. Further, loss of Pw1 in fibroblasts can enhance cardiac function, reduce cardiac fibrosis and extracellular matrix secretion after cardiac injury. To screen the targets of PW1, we contrasted chromatin immunoprecipitation (ChIP)-seq and RNA-seq using the injured left ventricles at 7 days post-MI, we next found PW1 binds directly upstream of the Pfas gene that encodes one of the DNPB enzymes phosphoribosylformylglycinamidine synthase (PFAS) in heart after injury. Similarly, specific knockout of pfas in fibroblasts also improves cardiac function and reduces ECM production. Moreover, de novo purine biosynthesis is necessary for ECM production in activated fibroblasts. These observations implicate understanding the mechanism of Pw1 in the repair of cardiac injury will provide new ideas for the treatment of cardiovascular diseases.
2024-12-04 | GSE232259 | GEO
Project description:The activation of fibroblasts and production of extracellular matrix (ECM) after cardiac injury has been the focus of research on cardiac fibrosis. Whether imprinted genes play a role in the fibrogenesis or extracellular matrix production after heart damage has not been studied. Here, we show that the imprinted gene Pw1 directed ECM production by regulating de novo purine synthesis (DNPB) after myocardial infarction (MI). After MI, the DNA methylation of the imprinting control region (ICR) of Pw1 gene in the injured area was reduced and both alleles of Pw1 in fibroblasts are activated. Further, loss of Pw1 in fibroblasts can enhance cardiac function, reduce cardiac fibrosis and extracellular matrix secretion after cardiac injury. To screen the targets of PW1, we contrasted chromatin immunoprecipitation (ChIP)-seq and RNA-seq using the injured left ventricles at 7 days post-MI, we next found PW1 binds directly upstream of the Pfas gene that encodes one of the DNPB enzymes phosphoribosylformylglycinamidine synthase (PFAS) in heart after injury. Similarly, specific knockout of pfas in fibroblasts also improves cardiac function and reduces ECM production. Moreover, de novo purine biosynthesis is necessary for ECM production in activated fibroblasts. These observations implicate understanding the mechanism of Pw1 in the repair of cardiac injury will provide new ideas for the treatment of cardiovascular diseases.
2024-12-04 | GSE232326 | GEO
Project description:The activation of fibroblasts and production of extracellular matrix (ECM) after cardiac injury has been the focus of research on cardiac fibrosis. Whether imprinted genes play a role in the fibrogenesis or extracellular matrix production after heart damage has not been studied. Here, we show that the imprinted gene Pw1 directed ECM production by regulating de novo purine synthesis (DNPB) after myocardial infarction (MI). After MI, the DNA methylation of the imprinting control region (ICR) of Pw1 gene in the injured area was reduced and both alleles of Pw1 in fibroblasts are activated. Further, loss of Pw1 in fibroblasts can enhance cardiac function, reduce cardiac fibrosis and extracellular matrix secretion after cardiac injury. To screen the targets of PW1, we contrasted chromatin immunoprecipitation (ChIP)-seq and RNA-seq using the injured left ventricles at 7 days post-MI, we next found PW1 binds directly upstream of the Pfas gene that encodes one of the DNPB enzymes phosphoribosylformylglycinamidine synthase (PFAS) in heart after injury. Similarly, specific knockout of pfas in fibroblasts also improves cardiac function and reduces ECM production. Moreover, de novo purine biosynthesis is necessary for ECM production in activated fibroblasts. These observations implicate understanding the mechanism of Pw1 in the repair of cardiac injury will provide new ideas for the treatment of cardiovascular diseases.
2024-12-04 | GSE279698 | GEO
Project description:The activation of fibroblasts and production of extracellular matrix (ECM) after cardiac injury has been the focus of research on cardiac fibrosis. Whether imprinted genes play a role in the fibrogenesis or extracellular matrix production after heart damage has not been studied. Here, we show that the imprinted gene Pw1 directed ECM production by regulating de novo purine synthesis (DNPB) after myocardial infarction (MI). After MI, the DNA methylation of the imprinting control region (ICR) of Pw1 gene in the injured area was reduced and both alleles of Pw1 in fibroblasts are activated. Further, loss of Pw1 in fibroblasts can enhance cardiac function, reduce cardiac fibrosis and extracellular matrix secretion after cardiac injury. To screen the targets of PW1, we contrasted chromatin immunoprecipitation (ChIP)-seq and RNA-seq using the injured left ventricles at 7 days post-MI, we next found PW1 binds directly upstream of the Pfas gene that encodes one of the DNPB enzymes phosphoribosylformylglycinamidine synthase (PFAS) in heart after injury. Similarly, specific knockout of pfas in fibroblasts also improves cardiac function and reduces ECM production. Moreover, de novo purine biosynthesis is necessary for ECM production in activated fibroblasts. These observations implicate understanding the mechanism of Pw1 in the repair of cardiac injury will provide new ideas for the treatment of cardiovascular diseases.
2024-12-04 | GSE231979 | GEO
Project description:Activation of imprinted gene Pw1 promotes cardiac fibrosis after ischemic injury
| PRJNA971616 | ENA
Project description:Activation of imprinted gene Pw1 promotes cardiac fibrosis after ischemic injury [sham_and_MI]
| PRJNA971501 | ENA
Project description:Activation of imprinted gene Pw1 promotes cardiac fibrosis after ischemic injury [ChIP-seq]
| PRJNA1174112 | ENA
Project description:Activation of imprinted gene Pw1 promotes cardiac fibrosis after ischemic injury [control_and_Pw1 CKO]
| PRJNA971619 | ENA
Project description:Activation of imprinted gene Pw1 promotes cardiac fibrosis after ischemic injury [control_and_Pfas CKO RNA-seq]
| PRJNA970349 | ENA
Project description:There is currently no therapy to limit the development of cardiac fibrosis and consequent heart failure. We have recently shown that cardiac fibrosis post-myocardial infarction (MI) can be regulated by resident cardiac cells with a fibrogenic signature and identified by the expression of PW1 (Peg3). Here we identify ?V-integrin (CD51) as an essential regulator of cardiac PW1+ cells fibrogenic behavior. We used transcriptomic and proteomic approaches to identify specific cell-surface markers for cardiac PW1+ cells and found that ?V-integrin (CD51) was expressed in almost all cardiac PW1+ cells (93%?±?1%), predominantly as the ?V?1 complex. ?V-integrin is a subunit member of the integrin family of cell adhesion receptors and was found to activate complex of latent transforming growth factor beta (TGF? at the surface of cardiac PW1+ cells. Pharmacological inhibition of ?V-integrin reduced the profibrotic action of cardiac PW1+CD51+ cells and was associated with improved cardiac function and animal survival following MI coupled with a reduced infarct size and fibrotic lesion. These data identify a targetable pathway that regulates cardiac fibrosis in response to an ischemic injury and demonstrate that pharmacological inhibition of ?V-integrin could reduce pathological outcomes following cardiac ischemia.
| S-EPMC7347632 | biostudies-literature