Basic fibroblast growth factor induces expression of the PDGF receptor-alpha on human bronchial smooth muscle cells

Bonner, James C.; Badgett, Annette; Lindroos, Pamela M.; Coin, P G

doi:10.1152/ajplung.1996.271.6.l880

Cited by 33 publications

(32 citation statements)

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“…38,40,53,54 Results presented in other studies show that PDGF-R␣ has an intrinsic ability to initiate negative signals, 39,41,55 but a direct inhibitory effect of PDGF-R␣ on growth factor and FCS activity has never been tested. In this regard it is noteworthy that bFGF is known to up-regulate PDGF-R␣ expression in smooth muscle cells 56,57 and that patch mice-ie, PDGF-R␣ knock-out mice-present severe alterations in the cardiovascular system. 58 Therefore, we hypothesized that PDGF-BB may play a negative modulating role in ECs, inhibiting the pro-angiogenic activity of bFGF, through PDGF-R␣ signaling.…”

Section: Discussionmentioning

confidence: 99%

Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor

Marchis

Ribatti

Giampietri

et al. 2002

Blood

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Basic fibroblast growth factor (bFGF) and platelet-derived growth factor-BB (PDGF-BB) modulate vascular wall cell function in vitro and angiogenesis in vivo. The aim of the current study was to determine how bovine aorta endothelial cells (BAECs) respond to the simultaneous exposure to PDGF-BB and bFGF. It was found that bFGF-dependent BAEC migration, proliferation, and differentiation into tubelike structures on reconstituted extracellular matrix (Matrigel) were inhibited by PDGF-BB. The role played by PDGF receptor ␣ (PDGF-R␣) was investigated by selective stimulation with PDGF-AA, by blocking PDGF-BB-binding to PDGF-R␣ with neomycin, or by transfecting cells with dominant-negative forms of the receptors to selectively impair either PDGF-R␣ or PDGF-R␤ function. In all cases, PDGF-R␣ impairment abolished the inhibitory effect of PDGF-BB on bFGF-directed BAEC migration. In addition, PDGF-R␣ phosphorylation was increased in the presence of bFGF and PDGF, as compared to PDGF alone, whereas mitogen-activated protein kinase phosphorylation was decreased in the presence of PDGF-BB and bFGF compared with bFGF alone. In vivo experiments showed that PDGF-BB and PDGF-AA inhibited bFGF-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane assay and that PDGF-BB inhibited bFGF-induced angiogenesis in Matrigel plugs injected subcutaneously in CD1 mice. Taken IntroductionThe endothelial layer represents a physical and chemical barrier between the vessel lumen and the underlying tissues. Endothelial cells (ECs) exert a variety of functions and modulate underlying smooth muscle cells by releasing molecules with vasoactive and growth-regulatory properties. 1 Endothelial cells present an active replication phenotype in vitro, but in vivo they are quiescent. 2 The different expression of membrane-bound receptors 3,4 and the in vivo action of specific inhibitors 5-7 may account, at least in part, for the different replication pattern observed.Basic fibroblast growth factor (bFGF) is a potent EC growth factor; it is known to induce a proangiogenic phenotype in ECs and is released under acidosis conditions that induce EC protection from apoptosis. 8 bFGF plays a critical role in physiologic and pathologic angiogenesis, including tumor angiogenesis. 9,10 It exerts its functions by direct action, 11 by inducing vascular endothelial growth factor (VEGF) synthesis, 12 or by potentiating VEGF activity. 13,14 Platelet-derived growth factor (PDGF) is a growth factor known to be active on ECs. Three PDGF isoforms have been identified as disulfide-linked dimers, namely PDGF-AA, PDGF-BB, and PDGF-AB, expressed by ECs under various conditions. 15-19 They interact with different affinity with 2 tyrosine-kinase receptors, PDGF-R␣ and PDGF-R␤, which are expressed on ECs in normal 4,20-22 and in pathologic conditions. [23][24][25][26] Recently, PDGF-C and PDGF-D isoforms were also identified. 27,28 PDGF isoforms are reported to exert mitogenic and chemotactic action on EC, although PDGF-AA appears to be less potent or inactive...

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Section: Discussionmentioning

confidence: 99%

Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor

Marchis

Ribatti

Giampietri

et al. 2002

Blood

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“…Various diverse stimuli have now been demonstrated to increase the proliferation of airway smooth muscle cells in cell culture, and have been reviewed in detail elsewhere [13,47,48]. Broadly, the substances now implicated in mitogenesis of airway smooth muscle, in addition to the action of serum itself (discussed in [49]), include pro-inflammatory mediators (histamine [46], 5-hydroxytryptamine (5-HT) [50], phenylephrine [51], tachykinins [52], endothelin (ET)-1 [53±56] and leukotriene D 4 [57]), several inflammatory cell-and plasma-derived enzymes (a-thrombin [58], tryptase [59], b-hexosaminidase and b-glucuronidase [60]), polypeptide growth factors (platelet-derived growth factor (PDGF) [61], epidermal growth factor (EGF) [62], fibroblast growth factor-2 (FGF-2) [63] and insulin-like growth factors (IGFs) [64]) and thromboxanes [65]. Pro-inflammatory cytokines (interleukin-1b [66], interleukin-6 [67], and tumour necrosis factor-a [68]) also induce a proliferative response in airway smooth muscle, which is revealed only under conditions of cyclo-oxygenase inhibition [69], in which the production and action of inhibitory prostanoids such as prostaglandin E 2 is limited.…”

Section: Mediators Of Airway Smooth Muscle Proliferationmentioning

confidence: 99%

Phenotypic diversity and molecular mechanisms of airway smooth muscle proliferation in asthma

Hirst¹,

Walker²,

Chilvers³

2000

Eur Respir J

109

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Chronic persistent asthma is characterized by poorly reversible airflow obstruction and airways inflammation and remodelling. Histopathological studies of airways removed at post mortem from patients with severe asthma reveal marked inflammatory and architectural changes associated with airway wall thickening. Increased airway smooth muscle content, occurring as a result of hyperplastic and/or hypertrophic growth, is believed to be one of the principal contributors to airway wall thickening. In recent years, significant advances have been made in elucidating the mediators and the intracellular pathways that regulate proliferation of airway smooth muscle. The contribution that smooth muscle makes to persistent airflow obstruction may not, however, be limited simply to its increased bulk within the airway wall. Interest is growing in the possibility that reversible phenotypic modulation and increased heterogeneity of airway smooth muscle function may also be a feature of the asthmatic airway. This review focuses on possible mechanisms controlling smooth muscle phenotype heterogeneity as well as on the mediators and intracellular pathways implicated in its cellular proliferation. Particular attention is paid to mechanisms involving activation of the extracellular signal regulated kinase‐, protein kinase C‐ and phosphoinositide 3‐kinase‐dependent pathways, since these appear to be the major candidate second messenger pathways for G protein‐ and tyrosine kinase‐coupled receptor‐stimulated proliferation.

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“…Several factors have been identified that may aid the phenotypic switch of airway SMCs, including platelet-derived growth factor (PDGF), epidermal growth factor, and basic fibroblast growth factor (2,3), and these factors have been shown to be elevated in the plasma of patients with asthma (4,5). Importantly, growth arrest of the proliferative/synthetic SMCs in culture restores the cells to a contractile phenotype (3).…”

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confidence: 99%

Retinoic Acid Inhibits Airway Smooth Muscle Cell Migration

Day

Lee²,

Park³

et al. 2006

Am J Respir Cell Mol Biol

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Airway remodeling in chronic asthma is characterized by increased smooth muscle mass that is associated with the reduction of the bronchial lumen as well as airway hyperresponsiveness. The development of agents that inhibit smooth muscle growth is therefore of interest for therapy to prevent asthma-associated airway remodeling. All-trans retinoic acid (ATRA) suppresses growth of vascular smooth muscle cells (SMCs) from the systemic and pulmonary circulation. The present study investigated the effects of ATRA on human bronchial (airway) SMCs. Human bronchial SMCs were found to express mRNAs for retinoic acid receptor (RAR)-␣, -␤, -␥, and retinoid X receptor (RXR)-␣, -␤, but not RXR-␥. Although ATRA was not effective in inhibiting proliferation or in inducing apoptosis in airway SMCs, we found that ATRA (0.2-2 M) inhibited the SMC migration in response to platelet-derived growth factor (PDGF), as determined in a modified Boyden chamber assay. Both RAR and RXR agonists also blocked PDGF-induced airway SMC migration. ATRA also inhibited PDGF-induced actin reorganization associated with migration. PDGF-induced actin reorganization and migration were blocked by inhibitors of phosphatidylinositol 3 kinase (PI3K) and Akt. However, migration was blocked by inhibitors of the MEK/ ERK pathway, with no effect on cytoskeletal reorganization. ATRA suppressed PDGF-induced Akt activation without influencing ERK activation. RAR was found to form protein-protein interactions with the p85 PI3K subunit. These results suggest that retinoic acid inhibits airway SMC migration through the modulation of the PI3K/Akt pathway.

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Basic fibroblast growth factor induces expression of the PDGF receptor-alpha on human bronchial smooth muscle cells

Cited by 33 publications

References 0 publications

Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor

Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor

Phenotypic diversity and molecular mechanisms of airway smooth muscle proliferation in asthma

Retinoic Acid Inhibits Airway Smooth Muscle Cell Migration

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