Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis

Rameshwar, Pranela; Joshi, Deval D.; Yadav, Prem N.; Qian, Jing; Gascón, Pedro; Chang, Victor; Anjaria, Devashish J.; Harrison, Jonathan S.; Song, Xiaosong

doi:10.1182/blood.v97.10.3025

Cited by 36 publications

(32 citation statements)

References 62 publications

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“…This protection could occur by SP's being able to down-regulate the expression of particular endopeptidases, such as CD13, and its complexing to a fibronectin, which is a relatively large molecule. 29,37 CD13 is the second enzyme following neutral endopeptidase that could degrade the carboxyl fragment of SP. 38 Reduced expression of CD13 would leave SP intact for hematopoietic stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…The cDNA for NK-1 was previously described. 29 NK-2 cDNA was prepared by RT-PCR with total RNA from BM stroma as template and the same primers as were used for quantitative RT-PCR (described above). The NK-2 fragment, which was equivalent to 274 base pairs, was subcloned into pNoTA/T7 (5 Prime 3 3 BLOOD, 1 NOVEMBER 2001 ⅐ VOLUME 98, NUMBER 9 For personal use only.…”

Section: Northern Analysismentioning

confidence: 99%

See 1 more Smart Citation

Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study

Joshi

Dang

Yadav

et al. 2001

Blood

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Section: Discussionmentioning

confidence: 99%

Section: Northern Analysismentioning

confidence: 99%

Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study

Joshi

Dang

Yadav

et al. 2001

Blood

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“…Competitive ELISA quantitated SP-IR as described (27). Briefly, 96-well plates were coated with a complex of streptavidin-biotinylated SP.…”

Section: Quantitation Of Sp-ir (Immunoreactive)mentioning

confidence: 99%

“…Cell extracts were prepared by repeated freeze-thaw cycles in a dry ice-ethanol bath. Total proteins were quantitated in cell extracts from stromal cultures using a kit from Bio-Rad (Hercules, CA), and 15 g was analyzed in Western blots for SP, HIF-1␣, or active caspase-3, as described (26,27). HIF-1␣ and active caspase-3 were electrophoresed on 15% SDS-PAGE and SP on 4 -20% gradient gel (Invitrogen, Carlsbad, CA).…”

Section: Immunoprecipitation and Western Blotsmentioning

confidence: 99%

Induction of Hypoxia-Inducible Factor-1α and Activation of Caspase-3 in Hypoxia-Reoxygenated Bone Marrow Stroma Is Negatively Regulated by the Delayed Production of Substance P

Qian

Ramroop²,

McLeod³

et al. 2001

The Journal of Immunology

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The bone marrow (BM), which is the major site of immune cell development in the adult, responds to different stimuli such as inflammation and hemorrhagic shock. Substance P (SP) is the major peptide encoded by the immune/hemopoietic modulator gene, preprotachykinin-1 (PPT-I). Differential gene expression using a microarray showed that SP reduced hypoxia-inducible factor-1α (HIF-1α) mRNA levels in BM stroma. Because long-term hypoxia induced the expression of PPT-I in BM mononuclear cells, we used timeline studies to determine whether PPT-I is central to the biologic responses of BM stroma subjected to 30-min hypoxia (pO2 = 35 mm Hg) followed by reoxygenation. HIF-1α mRNA and protein levels were increased up to 12 h. At this time, β-PPT-I mRNA was detected with the release of SP at 16 h. SP release correlated with down-regulation of HIF-1α to baseline. A direct role for SP in HIF-1α expression was demonstrated as follows: 1) transient knockout of β-PPT-I showed an increase in HIF-1α expression up to 48 h of reoxygenation; and 2) HIF-1α expression remained baseline during reoxygenation when stroma was subjected to hypoxia in the presence of SP. Reoxygenation activated the PPT-I promoter with concomitant nuclear translocation of HIF-1α that can bind to the respective consensus sequences within the PPT-I promoter. SP reversed active caspase-3, an indicator of apoptosis and erythropoiesis, to homeostasis level after reoxygenation of hypoxic stroma. The results show that during reoxgenation the PPT-I gene acts as a negative regulator on the expression of HIF-1α and active caspase-3 in BM stroma subjected to reoxygenation.

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“…This interaction results from the structural similarity between regions of fibronectin and the NK-1 receptor [25]. The mimicry between regions of fibronectin and NK-1 allows substance P to interact with fibronectin and evade degradation.…”

Section: Substance P: Background and Link To Myelofibrosismentioning

confidence: 99%

Substance P-Fibronectin-Cytokine Interactions in Myeloproliferative Disorders with Bone Marrow Fibrosis

Rameshwar

Yook

et al. 2002

Acta Haematol

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Bone marrow (BM) fibrosis could occur secondarily to several clinical disorders: hematological and nonhematological. Clinical presentation of fibrosis could occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome and myeloma. The pathophysiology underlying BM fibrosis remains unclear despite intensive study, with a corresponding lack of specific therapy. This review discusses new insights in the role of substance P, cytokines and fibronectin in the development of BM fibrosis. Substance P is a neuropeptide that possesses pleiotropic properties, e.g. neurotransmission and immune/hematopoietic modulation and is linked to BM fibrosis. Cytokines and growth factors, in particular those associated with fibrogenic properties, e.g. TGF-β, IL-1 and platelet-derived growth factor, are linked to BM fibrosis. Extracellular matrix proteins are increased in patients with BM fibrosis. Fibronectin in the sera of patients with BM fibrosis is complexed to substance P. Fibronectin appears to protect substance P from degradation by endogenous peptidases. This review describes the preliminary findings on the colocalization of substance P and fibronectin in the BM of patients with fibrosis. These data are reviewed in the context of published reports with particular focus on the relevant cytokines. A more detailed understanding of intra- and intercellular mechanisms in BM fibrosis may lead to effective therapy.

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Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis

Cited by 36 publications

References 62 publications

Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study

Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study

Induction of Hypoxia-Inducible Factor-1α and Activation of Caspase-3 in Hypoxia-Reoxygenated Bone Marrow Stroma Is Negatively Regulated by the Delayed Production of Substance P

Substance P-Fibronectin-Cytokine Interactions in Myeloproliferative Disorders with Bone Marrow Fibrosis

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