| Id |
Subject |
Object |
Predicate |
Lexical cue |
| BEL:20080818 |
0-1708 |
p(HGNC:IL13) increases tscript(p(HGNC:STAT6)) |
denotes |
Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.
IL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) fibroblasts and yet enhanced Egr-1 mRNA and protein levels in Stat1(-/-) fibroblasts. Our findings support the hypothesis that Stat6 and Stat1 exert stimulatory and inhibitory effects on Egr-1 and PDGF ligand mRNA transcription, respectively. This novel mechanism could aid in identifying molecular targets for the treatment of chronic airway remodeling and fibrosis in asthma |
| BEL:20067684 |
0-1331 |
tscript(p(MGI:Egr1)) increases r(MGI:Pdgfa) |
denotes |
Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.
IL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) |
| BEL:20067684 |
0-1331 |
tscript(p(MGI:Egr1)) increases r(MGI:Pdgfa) |
denotes |
Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.
IL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) |
| BEL:20067686 |
0-1331 |
tscript(p(MGI:Egr1)) increases r(MGI:Pdgfc) |
denotes |
Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.
IL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) |
| BEL:20067686 |
0-1331 |
tscript(p(MGI:Egr1)) increases r(MGI:Pdgfc) |
denotes |
Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.
IL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) |
| BEL:20054316 |
0-1573 |
p(MGI:Il13) increases p(MGI:Pdgfc) |
denotes |
Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.
IL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) fibroblasts and yet enhanced Egr-1 mRNA and protein levels in Stat1(-/-) fibroblasts. Our findings support the hypothesis that Stat6 and Stat1 exert stimulatory and inhibitory effects on Egr-1 and PDGF ligand mRNA transcription, respectively |
| BEL:20054324 |
202-1331 |
p(MGI:Il13) increases p(MGI:Stat1,pmod(P,Y)) |
denotes |
way remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) |
| BEL:20054326 |
0-1331 |
p(MGI:Il13) increases p(MGI:Stat6,pmod(P,Y)) |
denotes |
Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.
IL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) |
| BEL:20054412 |
39-1708 |
p(MGI:Il13) increases r(MGI:Pdgfa) |
denotes |
IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.
IL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) fibroblasts and yet enhanced Egr-1 mRNA and protein levels in Stat1(-/-) fibroblasts. Our findings support the hypothesis that Stat6 and Stat1 exert stimulatory and inhibitory effects on Egr-1 and PDGF ligand mRNA transcription, respectively. This novel mechanism could aid in identifying molecular targets for the treatment of chronic airway remodeling and fibrosis in asthma |
| BEL:20054414 |
39-1708 |
p(MGI:Il13) increases r(MGI:Pdgfc) |
denotes |
IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts.
IL-13 is a key cytokine involved in airway remodeling in asthma. We previously reported that IL-13 stimulated the mitogenesis of lung fibroblasts via platelet-derived growth factor (PDGF)-AA. In this report, we show that IL-13 increases PDGF-A and PDGF-C mRNA levels through a dual intracellular cascade that requires coactivation of Stat6 and Stat1 to impact transcriptional regulation of the early growth response (Egr)-1 gene, which then drives PDGF expression. Increased levels of PDGF-AA and PDGF-CC protein were observed in vivo in the airways of IL-13 transgenic mice. IL-13 up-regulated PDGF-A and PDGF-C mRNA levels in lung fibroblasts isolated from three different background strains of mice. However, IL-13-induced PDGF-A and PDGF-C mRNA levels were significantly reduced in Stat6-deficient (Stat6(-/-)) fibroblasts as compared with wild-type Stat6(+/+) fibroblasts. In contrast, IL-13-induced PDGF-A and PDGF-C mRNAs were enhanced in Stat1(-/-) fibroblasts as compared with Stat1(+/+) fibroblasts. IL-13 did not up-regulate PDGF-A or PDGF-C mRNA levels in Egr-1(-/-) fibroblasts. Moreover, IL-13 did not increase Egr-1 mRNA and protein levels in Stat6(-/-) fibroblasts and yet enhanced Egr-1 mRNA and protein levels in Stat1(-/-) fibroblasts. Our findings support the hypothesis that Stat6 and Stat1 exert stimulatory and inhibitory effects on Egr-1 and PDGF ligand mRNA transcription, respectively. This novel mechanism could aid in identifying molecular targets for the treatment of chronic airway remodeling and fibrosis in asthma |
