Platelet‐derived growth factor AA homodimer is the predominant isoform in human platelets and acute human wound fluid

Soma, Yoshinao; Dvonch, Victoria; Grotendorst, Gary R.

doi:10.1096/fasebj.6.11.1644262

Cited by 51 publications

(24 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the human acute and chronic wounds in our study, PDGF-BB and PDGF-AB were considerably less prevalent than PDGF-AAL. A recent study that analyzed acute human wound fluid also found predominantly PDGF-AA (12). Another study in which wound fluid from chronic pressure ulcers was analyzed found variable amounts of PDGF present, but the assay was unable to discriminate among the isoforms (49).…”

Section: Discussionmentioning

confidence: 95%

“…These diverse cell types migrate, proliferate, and differentiate, eventually producing a collagen-containing scar. Specific growth factors are believed to regulate these processes because cell types found within wounds both synthesize and bear receptors for a variety of growth factors in vitro (8)(9)(10)(11)(12)(13)(14)(15)(16)(17), and growth factors pharmacologically applied to wounds can accelerate in vivo repair (2,3,5,6,10,(18)(19)(20)(21)(22)(23). Growth factors have also been implicated in the pathogenesis of lesions of the vascular wall and in tumor growth, consistent with the notion that these pathophysiologic processes share commonalities with normal tissue repair processes (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Pierce¹,

Tarpley²,

Tseng³

et al. 1995

J. Clin. Invest.

217

137

View full text Add to dashboard Cite

Some human chronic dermal wounds treated with recombinant platelet-derived growth factor-BB (rPDGF-BB) show increased healing coupled with fibroblast activation and granulation tissue formation. To determine whether endogenous PDGF is associated with healing and nonhealing dermal ulcer phenotypes, we developed monoclonal antibodies capable of recognizing the three isoforms of PDGF, AA, AB, and BB dimers, and capable of discriminating between two alternatively spliced A chain transcripts. We detected little PDGF isoform expression in normal skin and in nonhealing dermal ulcers. In contrast, in surgically created acute wounds and chronic ulcers treated with rPDGF-BB, markedly upregulated levels of PDGF-AA (long form) were found. In both types of wounds, increased PDGF-AA was detected primarily in capillaries and fibroblasts, although in rPDGF-BB-treated chronic wounds, widespread expression of PDGF-AA was somewhat delayed. With continued treatment, the long form of PDGF-AA, which can preferentially bind extracellular matrix, was expressed only in capillaries, while fibroblasts began synthesizing the short form of PDGF-AA. Within capillaries, all endothelial cells and varying numbers of pericytes and smooth muscle cells contained PDGF-AA. In all wounds, macrophages and keratinocytes were not a major contributor. While PDGF-BB and PDGF-AB were present in a minority of healing wounds, they were usually present at lower levels than PDGF-AA. PDGF-18 receptors, which bind only PDGF-BB and not other isoforms, were found in normal skin and granulation tissue, providing a molecular basis for treating human chronic wounds with exogenous rPDGF-BB. (J. Clin.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Pierce¹,

Tarpley²,

Tseng³

et al. 1995

J. Clin. Invest.

217

137

View full text Add to dashboard Cite

show abstract

“…However, in our cohort of subjects a large proportion (58%) of PM with positive PDGF levels was not associated with thrombocytosis. Furthermore, the largest part of PDGF produced by platelets is made up of AA homodimers rather than AB heterodimers [28] . In addition, activated platelets have a limited place in the release of PDGF in hemorrhagic malignant pleural effusions [6] .…”

Section: Discussionmentioning

confidence: 99%

Serum PDGF-AB in Pleural Mesothelioma

Filiberti¹,

Marroni²,

Neri³

et al. 2005

Tumor Biol

View full text Add to dashboard Cite

Overexpression of platelet-derived growth factor (PDGF) has been observed in lung and pleural tumors. The aim of this study was to evaluate the diagnostic and prognostic role of serum PDGF in pleural mesothelioma (PM). Four groups of subjects were studied: 93 malignant PM patients, 33 primary non small cell lung cancer patients, 51 subjects exposed to asbestos, defined as high-risk controls, and 24 healthy controls. PDGF-AB mean concentration was higher in PM patients (45.8 ng/ml) than in high-risk controls (33.1 ng/ml) and healthy controls (26.8 ng/ml). Using the cut-off level of 49.8 ng/ml, corresponding to the mean + 2SD of PDGF-AB in healthy controls, 43% of PM patients showed positive PDGF-AB levels. Survival was evaluated in 82 PM patients. At the end of the follow-up (median 9.8 months) 80.5% of patients had died. Median survival was 13.1 and 7.9 months for patients with PDGF-AB lower and higher than the cut-off, respectively. Adjusting for age, sex, histology and platelet count, positive PDGF-AB levels were associated with lower survival (OR = 1.2, 95%CI: 0.9–1.6), even if not significantly so. In conclusion, serum PDGF may represent a useful additional parameter to prognostic factors already available for PM.

show abstract

“…The A chain and the B chain are encoded by separated but related genes. Molecular cloning of the PDGF A and B genes has been reported by several groups [31][32][33][34][35][36][37]. Approximately 70% of the PDGF purified from human platelets consists of PDGF-AB and the rest is mainly PDGF-BB [38].…”

Section: Pdgf: Chemical Nature Storage and Releasementioning

confidence: 99%

Platelets and inflammation: Role of platelet-derived growth factor, adhesion molecules and histamine

1997

View full text Add to dashboard Cite

Despite the fact that the relationship between platelets and the inflammatory and immune responses has been reviewed previously, the allocation of platelets among the inflammatory cells is still at issue. Recent developments in our understanding of platelet-associated signalling events have offered new potential insights into platelet functions in inflammatory and immune-related diseases. In recent years, it has been established that a range of molecules, mainly associated with the platelet surface and/or the platelet granules, regulate the capacity of platelets to cross-talk with other inflammatory cells during the process of inflammation, and of vascular inflammation in particular. This is the case with platelet-derived growth factor (PDGF), secreted from platelet alpha-granules, with P-selectin, expressed on the platelet surface, and with platelet histamine, which is secreted from platelets in response to aggregatory and inflammatory stimuli. The nature and mechanism of action of these regulatory molecules, physiologically present in platelets and mobilised upon platelet activation and aggregation, is the subject of this review. The participation of platelets, through PDGF, P-selectin and histamine, is also discussed in overtly inflammatory disorders, such as acute respiratory distress syndrome, mesangial glomerulonephritis, chronic inflammatory bowel disease, disseminated intravascular inflammation, and allergic vasculitis, focusing on possible pharmacological interventions specifically active against growth factors, adhesion molecules and platelet histamine.

show abstract

Platelet‐derived growth factor AA homodimer is the predominant isoform in human platelets and acute human wound fluid

Cited by 51 publications

References 22 publications

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Serum PDGF-AB in Pleural Mesothelioma

Platelets and inflammation: Role of platelet-derived growth factor, adhesion molecules and histamine

Contact Info

Product

Resources

About