Platelet-Derived Growth Factor C in Alcoholics

2020 ◽  
Vol 55 (2) ◽  
pp. 157-163 ◽  
Author(s):  
C Martín-González ◽  
L González-Navarrete ◽  
I Ribot-Hernández ◽  
V Vera-Delgado ◽  
J Alvisa-Negrín ◽  
...  

Abstract Aims Platelet-derived growth factor (PDGF) promotes liver collagen deposition, acting on hepatic stellate cells. Despite this, low serum PDGF levels were reported in chronic hepatitis C or B infection, although some studies yield the opposite result. Since PDGF may be related not only to fibrosis but also with vascular, neuronal or muscle disease, it is important to analyze its behavior in alcoholics. Methods In total, 17 controls and 62 alcoholic patients consecutively admitted to the hospitalization unit of the Internal Medicine Service were included. We determined serum levels of PDGF C, routine laboratory evaluation, tumor necrosis factor-α, interleukin (IL)-6 and IL-8 and malondialdehyde (MDA) levels. We analyzed the relationships between PDGF and liver function, ethanol intake and inflammatory reaction by both univariate and multivariate analysis to discern which variables PDGF levels depend on. Results Serum PDGF levels were significantly lower among patients (675 ± 466 pg/ml) than among controls (1074 ± 337 pg/ml; Z = 3.70; P < 0.001), and even lower among cirrhotics (549 ± 412 among cirrhotics vs 778 ± 487 among non-cirrhotics; Z = 2.33; P = 0.02). PDGF levels showed a direct correlation with prothrombin activity (ρ = 0.50; P < 0.001), platelet count (ρ = 0.44; P < 0.001) and inverse ones with bilirubin (ρ = −0.39; P = 0.002), IL-6 (ρ = −0.33; P = 0.016), IL-8 (ρ = −0.47; P < 0.001), and MDA levels (ρ = −0.44; P < 0.001). By multivariate analysis, only prothrombin activity and platelet count were independently related to PDGF. Conclusion PDGF-C levels are decreased in alcoholics, especially among cirrhotics. Multivariate analysis discloses that only prothrombin activity and platelet count are independently related to PDGF-C levels.

2020 ◽  
Vol 21 (7) ◽  
pp. 2360 ◽  
Author(s):  
Li-Han Lin ◽  
Jiun-Sheng Lin ◽  
Cheng-Chieh Yang ◽  
Hui-Wen Cheng ◽  
Kuo-Wei Chang ◽  
...  

Oral squamous cell carcinoma (OSCC) is a cancerous disease with poor prognosis. According to the statistics, the 5-year survival rate has not improved significantly over the past 20 years. The platelet-derived growth factor (PDGF) and its signaling pathway is a key regulator of angiogenesis and tumorigenesis. High level of PDGF and its receptor (PDGFR) have been reported in several types of malignancies. In this study, we investigated the relationship of the molecular expression levels of PDGF and PDGFR with clinicopathological parameters in OSCC. To this end, we measured the mRNA and protein levels of PDGF and PDGFR by real-time quantitative PCR (qRT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA), respectively. We found positive correlations of the mRNA levels of PDGFA, PDGFB, and PDGFRB with lymph node metastasis and poor overall survival (OS). High expression of PDGF, PDGFRA, and PDGFRB were remarkably associated with lymph node metastasis and poor OS, as determined by immunohistochemistry. Preoperative serum levels of PDGF-AA and PDGF-BB had a positive correlation with preoperative platelet count. Elevated serum levels of PDGF-AA. PDGF-BB, and platelet count correlated with lymph node metastasis and an unfavorable outcome. In multivariate Cox regression analysis, PDGFA mRNA, PDGFB mRNA, PDGFRB mRNA, PDGF immunoexpression, PDGFRB immunoexpression, serum PDGF-AA, serum PDGF-BB, and platelet count emerged as significant independent prognostic factors for OS. In vitro, we found that elevated PDGF promotes colony formation, migration, and invasiveness of SAS and OECM-1 cancer cell lines. Our results suggest that the expression level of serum PDGF has the potential to become a useful diagnostic marker for the prognosis of OSCC. In addition, PDGFR should be considered as a potential therapeutic target for OSCC. Furthermore, research should be undertaken to elucidate the role of PDGF and PDGFR regarding the behavior of tumor cells in OSCC.


Author(s):  
Simona Simone ◽  
Annarita Chieti ◽  
Paola Pontrelli ◽  
Federica Rascio ◽  
Giuseppe Castellano ◽  
...  

Abstract Background Hemodialysis patients present a dramatic increase in cardiovascular morbidity/mortality. Circulating immune cells, activated by both uremic milieu and dialysis, play a key role in the pathogenesis of dialysis-related vascular disease. The aim of our study was to identify, through a high-throughput approach, differences in gene expression profiles in the peripheral blood mononuclear cells (PBMCs) of patients treated with on-line hemodiafiltration and bicarbonate hemodialysis. Methods The transcriptomic profile was investigated in PBMCs isolated from eight patients on on-line hemodiafiltration and eight patients on bicarbonate hemodialysis by microarray analysis. The results were evaluated by statistical and functional pathway analysis and validated by real time PCR (qPCR) in an independent cohort of patients (on-line hemodiafiltration N = 20, bicarbonate hemodialysis n = 20). Results Eight hundred and forty-seven genes were differentially expressed in patients treated with  on-line hemodiafiltration and bicarbonate hemodialysis. Thirty-seven functional gene networks were identified and atherosclerosis signaling was the top canonical pathway regulated by on-line hemodiafiltration. Among the genes of this pathway, on-line hemodiafiltration was associated with a reduced expression of Platelet-derived growth factor A chain (PDGF A), Clusterin, Monoamine Oxidase A, Interleukin-6 (IL-6) and Vascular Endothelial Growth Factor C (VEGF-)C and with an increase of Apolipoprotein E. qPCR confirmed the microarray results. Platelet derived growth factor AA (PDGF-AA), IL-6 and VEGF-C serum levels were significantly lower in the on-line hemodiafiltration group. Finally, 10 patients previously on bicarbonate hemodialysis  were switched to on-line hemodiafiltration and PBMCs were harvested after 6 months. The qPCR results from this perspective group confirmed the modulation of atherosclerotic genes observed in the cross-sectional analysis. Conclusions Our data suggest that type of dialysis (on-line hemodiafiltration versus bicarbonate hemodialysis) may modulate the expression of several genes involved in the pathogenesis of atherosclerotic disease.


2005 ◽  
Vol 102 (9) ◽  
pp. 3389-3394 ◽  
Author(s):  
J. S. Campbell ◽  
S. D. Hughes ◽  
D. G. Gilbertson ◽  
T. E. Palmer ◽  
M. S. Holdren ◽  
...  

2001 ◽  
pp. 271-276 ◽  
Author(s):  
H Morita ◽  
M Mizutori ◽  
K Takeuchi ◽  
S Motoyama ◽  
T Maruo

OBJECTIVE: To elucidate the role of platelet-derived growth factor (PDGF) in the pathophysiology of pregnancy-induced hypertension (PIH) in which the spiral arteries of the decidua demonstrate the atherosclerotic change. DESIGN AND METHODS: We determined serum levels of PDGF and PDGF expression in the decidua as well as serum levels of 17 beta-estradiol (E2) and progesterone (P4) both in normotensive cases and in PIH cases. Furthermore, we investigated whether sex steroid hormones could interact with PDGF in cultured vascular smooth muscle cells (SMC) by immunohistochemical staining for proliferating cell nuclear antigen. RESULTS: Serum PDGF levels were higher (P<0.01) but serum E2 levels were lower (P<0.01) in PIH cases compared with normotensive cases. There was no statistically significant difference between serum P4 levels in PIH cases and those in normotensive cases. Immunohistochemical staining for PDGF in SMC of spiral arteries was more prominent in PIH cases than in normotensive cases. The proliferative potential of cultured SMC was stimulated by PDGF, but inhibited by concomitant treatment with PDGF and E2. CONCLUSIONS: PDGF is suggested to play an important role in the pathophysiology of PIH through its stimulatory effect on vascular SMC proliferation which may elicit the atherosclerotic change in the spiral arteries of the placenta.


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