Role of natriuretic peptide signaling in modulating asthma and inflammationThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

Mohapatra, Shyam S.

doi:10.1139/y07-066

Cited by 22 publications

(8 citation statements)

References 66 publications

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“…In addition, the JNK and p38 have been suggested to elicite functions beyond that of activating proliferation, such as mediating responses to cell stresses and the extracellular environment [15, 16]. The fact that ANP inhibits these MAPKs, which provide possible mechanisms through which ANP may stimulate anti-inflammatory signals [7, 9, 29, 30]. …”

Section: Discussionmentioning

confidence: 99%

“…In addition, ANP has been proven to potently inhibit cell growth and proliferation under both physiological and pathophysiological conditions, such as cardiac hypertrophy and the metastasis of cancer cells [5–7]. ANP belongs to the natriuretic peptide family comprised of three peptide hormones: ANP, brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) and all three hormones are encoded by separate gene [8].…”

Section: Introductionmentioning

confidence: 99%

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Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes the vascular endothelial growth factor-stimulated MAPKs and downstream effectors AP-1 and CREB in mouse mesangial cells

Tripathi

Pandey

2012

Mol Cell Biochem

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Along with its natriuretic, diuretic, and vasodilatory properties, atrial natriuretic peptide (ANP) and its guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) exhibit an inhibitory effect on cell growth and proliferation. However, the signaling pathways mediating this inhibition are not well understood. The objective of this study was to determine the effect of ANP-NPRA system on mitogen-activated protein kinases (MAPKs) and the downstream proliferative transcription factors involving activating protein-1 (AP-1) and cAMP-response element binding protein (CREB) in agonist-stimulated mouse mesangial cells (MMCs). We found that ANP inhibited vascular endothelial growth factor (VEGF)-stimulated phosphorylation of MAPKs (Erk1, Erk2, JNK, and p38), to a greater extent in NPRA-transfected cells (50–60%) relative to vector-transfected cells (25–30%). The analyses of the phosphorylated transcription factors revealed that ANP inhibited VEGF-stimulated activation of CREB, and the AP-1 subunits (c-jun and c-fos). Gel shift assays demonstrated that ANP inhibited VEGF-stimulated AP-1 and CREB DNA-binding ability by 67 % and 62 %, respectively. The addition of the protein kinase G (PKG) inhibitor, KT-5823, restored the VEGF-stimulated activation of MAPKs, AP-1, and CREB, demonstrating the integral role of cGMP/PKG signaling in NPRA-mediated effects. Our results delineate the under lying mechanisms through which ANP-NPRA system exerts an inhibitory effect on MAPKs and down-stream effector molecules, AP-1 and CREB, critical for cell growth and proliferation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes the vascular endothelial growth factor-stimulated MAPKs and downstream effectors AP-1 and CREB in mouse mesangial cells

Tripathi

Pandey

2012

Mol Cell Biochem

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“…For example, atrial natriuretic peptide (ANP, encoded by Nappa) is up-regulated during post-pneumonectomy lung regeneration, but down-regulated in OVA-induced asthma, a process associated with a fibrotic response [26]. ANP is anti-fibrotic, and acts through inhibition of Tgfβ-induced fibroblast transformation [27]. The combined effects of different growth factors can also modulate the actions of Tgfβ on cell proliferation and collagen production in fibroblast trans-differentiation.…”

Section: Discussionmentioning

confidence: 99%

Global gene expression patterns in the post-pneumonectomy lung of adult mice

et al. 2009

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BackgroundAdult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration.MethodsUnilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points). Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days) and analyzed using microarray technology.ResultsThe observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1), as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis.ConclusionThese data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.

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“…These include: relaxation of airway smooth muscle (ASM), attenuation of airway inflammation and hyper-responsiveness, inhibition of proliferation of ASM, regulation of lung permeability, surfactant production and recovery from exercise [13–20]. Recent data link single nucleotide polymorphisms (SNPs) of NPPA, the gene coding for ANP, to asthma susceptibility [21,22].…”

Section: Introductionmentioning

confidence: 99%

“…Recent data link single nucleotide polymorphisms (SNPs) of NPPA, the gene coding for ANP, to asthma susceptibility [21,22]. Furthermore, preclinical in vitro and in vivo studies demonstrate beneficial bronchodilation and anti-inflammatory effects of ANP and BNP [13,15,19,20,23–25]. …”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo pharmacological profile of PL-3994, a novel cyclic peptide (Hept-cyclo(Cys-His-Phe-d-Ala-Gly-Arg-d-Nle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg mimetic]-NH2) natriuretic peptide receptor-A agonist that is resistant to neutral endopeptidase and acts as a bronchodilator

Edelson

Makhlina

Silvester

et al. 2013

Pulmonary Pharmacology & Therapeutics

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The pharmacological and airways relaxant profiles of PL-3994 (Hept-cyclo(Cys-His-Phe-d-Ala-Gly-Arg-dNle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg mimetic]-NH2), a novel natriuretic peptide receptor-A (NPR-A) agonist, were evaluated. PL-3994, a full agonist, has high affinity for recombinant human (h), dog, or rat NPR-As (Kis of 1, 41, and 10 nm, respectively), and produced concentration-dependent cGMP generation in human, dog and rat NPR-As (respective EC50s of 2, 3 and 14 nm). PL-3994 has a Ki of 7 nm for hNPR-C but was without effect on cGMP generation in hNPR-B. PL-3994 (1 µm) was without significant effect against 75 diverse molecular targets. PL-3994 or BNP, a natural NPR ligand, produced concentration-dependent relaxation of pre-contracted guinea-pig trachea (IC50s of 42.7 and 10.7 nm, respectively). PL-3994, and also BNP, (0.1 nm–100 µm) elicited a potent, concentration-dependent but small relaxation of pre-contracted human precision-cut lung slices (hPCLS). Intratracheal PL-3994 (1–1000 µg/kg) produced a dose-dependent inhibition of the bronchoconstrictor response evoked by aerosolized methacholine, but was without significant effect on cardiovascular parameters. PL-3994 was resistant to degradation by human neutral endopeptidase (hNEP) (92% remaining after 2 h), whereas the natural ligands, ANP and CNP, were rapidly metabolized (≤1% remaining after 2 h). PL-3994 is a potent, selective NPR agonist, resistant to NEP, with relaxant effects in guinea-pig and human airway smooth muscle systems. PL-3994 has the profile predictive of longer clinical bronchodilator activity than observed previously with ANP, and suggests its potential utility in the treatment of asthma, in addition to being a useful research tool to evaluate NPR biology.

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Role of natriuretic peptide signaling in modulating asthma and inflammationThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

Cited by 22 publications

References 66 publications

Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes the vascular endothelial growth factor-stimulated MAPKs and downstream effectors AP-1 and CREB in mouse mesangial cells

Guanylyl cyclase/natriuretic peptide receptor-A signaling antagonizes the vascular endothelial growth factor-stimulated MAPKs and downstream effectors AP-1 and CREB in mouse mesangial cells

Global gene expression patterns in the post-pneumonectomy lung of adult mice

In vitro and in vivo pharmacological profile of PL-3994, a novel cyclic peptide (Hept-cyclo(Cys-His-Phe-d-Ala-Gly-Arg-d-Nle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg mimetic]-NH2) natriuretic peptide receptor-A agonist that is resistant to neutral endopeptidase and acts as a bronchodilator

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