scholarly journals Characterization of the molecular mechanism involved in the activation of hyaluronan synthetase by platelet-derived growth factor in human mesothelial cells

1992 ◽  
Vol 283 (1) ◽  
pp. 165-170 ◽  
Author(s):  
P Heldin ◽  
T Asplund ◽  
D Ytterberg ◽  
S Thelin ◽  
T C Laurent
Keyword(s):  
Growth Factor ◽  
Molecular Mechanism ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mesothelial Cells ◽  
Platelet Derived Growth Factor ◽  
Synthetase Activity ◽  
Normal Human ◽  
Stimulation Of

The molecular mechanism involved in the stimulation of hyaluronan synthetase in normal human mesothelial cells was investigated. Exposure of mesothelial cells to platelet-derived growth factor (PDGF)-BB stimulated hyaluronan synthetase activity, measured in isolated membrane preparations, as well as hyaluronan secretion into the medium. The effect on hyaluronan synthetase was maximal after 6 h of treatment. In contrast, the stimulatory effect of transforming growth factor-beta 1 reached a maximum after 24 h. The stimulatory effect of PDGF-BB was inhibited by cycloheximide. The phosphotyrosine phosphatase inhibitor vanadate was found to stimulate hyaluronan synthetase activity, and to potentiate the effect of PDGF-BB. The protein kinase C (PKC) stimulator phorbol 12-myristate 13-acetate (PMA) also stimulated hyaluronan synthetase; furthermore, depletion of PKC by preincubation of the cells with PMA led to an inhibition of the PDGF-BB-induced stimulation of hyaluronan synthetase activity. Thus the PDGF-BB-induced stimulation of hyaluronan synthetase activity is dependent on protein synthesis and involves tyrosine phosphorylation and activation of PKC.

scholarly journals Pengaruh pemberian plasma kaya trombosit dan karbonat hidroksiapatit pada proses penutupan defek tulang kepala hewan coba tikus

2016 ◽  
Vol 8 (3) ◽  
Author(s):  
Lucia Nirmalasari ◽  
Maximillian Ch. Oley ◽  
Eko Prasetyo ◽  
Mendy Hatibie ◽  
Lily L. Loho
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Rattus Norvegicus ◽  
Transforming Growth Factor ◽  
Platelet Rich Plasma ◽  
Platelet Derived Growth Factor ◽  
Vascular Endothelial ◽  
Angiogenesis Factor ◽  
Growth Factor Beta ◽  
Endothelial Growth Factor

Abstract: Recently, platelet rich plasma has been popular and its use has begin on human in developed countries. Platelet rich plasma is defined as autologus blood with concentration of platelets three to five times above baseline level, which contains at least seven growth factors like Platelet Derived Growth Factor (PDGF), Platelet Derived Angiogenesis Factor (PDAF), Platelet Derived Endothelial Growth Factor (PDEGF), Transforming Growth Factor Beta (TGF- β), Insulin like Growth Factor (IGF), Fibroblast Growth Factor (FGF), and Vascular Endothelial Growth Factor (VEGF). The golden standard for reconstruction of cranial bone defects demonstrates osteoconduction scaffold, osteoinduction like growth factors, and osteogenesis. Alloplastic biomaterials have revolutionalized craniofacial reconstruction. Carbonated hydroxyapatite (CHA) has been studied for years as implant material due to its similarity with the mineral component of bone. In this study we investigated and compare the effects of PRP and CHA on bone regeneration in rat cranial defects. This was an experimental study with a true experimental design on white male rats (Rattus norvegicus). Cranial deffects of 3 mm diameter were created in rat cranium and grafted with CHA and PRP combination, CHA alone, and control. The relationships among them were analyzed by using Mann Whitney and SPSS Statistics Program Package Version 22.0. The results showed that the experimental group of 2 weeks had no different between inflammatory reaction (P = 0.119), woven bone (P = 0.094) and lamellar bone (P = 0.130). At 4 weeks,a combination of PRP and CHA showed a superior growth of lamellar bone compared to CHA (P = 0.009). Conclusion: A combination of PRP and CHA in bone regeneration showed a histological tendency toward increased bone formation. However, future investigations should be conducted in different period times.Keywords: platelet rich plasma, carbonated hydroxyapatite, cranial defectAbstrak: Plasma kaya trombosit makin banyak digunakan dalam dunia kedokteran. Di negara maju pengunaannya sudah mulai diteliti pada manusia. Plasma kaya trombosit adalah fraksi plasma darah dengan konsentrasi platelet 3-5 kali diatas nilai normal yang mengandung sekurang-kurangnya 7 faktor pertumbuhan, diantaranya Platelet Derived Growth Factor (PDGF), Platelet Derived Angiogenesis Factor (PDAF), Platelet Derived Endothelial Growth Factor (PDEGF), Transforming Growth Factor Beta (TGF- β), Insulin like Growth Factor (IGF), Fibroblast Growth Factor (FGF), dan Vascular Endothelial Growth Factor (VEGF) yang dapat meningkatkan proses osteogenesis. Karbonat hidroksiapatit adalah material pengganti tulang yang dapat mempercepat regenerasi jaringan tulang serta memiliki kandungan kalsium,fosfat dan karbonat yang mirip dengan tulang manusia. Tulang yang tumbuh pada awal berupa tulang muda yang memiliki serat kolagen yang tidak teratur dan banyak osteosit disebut tulang imatur. Tulang imatur kemudian akan diganti oleh tulang matur yang memiliki serabut kolagen yang teratur. Jenis penelitian ini ialah eksperimental pada 36 hewan coba tikus putih wistar (Rattus norvegicus). Defek kalvaria pada tikus dengan diameter 3 mm diisi sesuai perlakuan: plasma kaya trombosit dengan karbonat hidroksiapatit, karbonat apatit tunggal, dan kontrol. Plasma kaya trombosit dibuat dari autologus darah tikus yang diberi perlakuan plasma kaya trombosit serta karbonat hidroksiapatit dan karbonat apatit tunggal. Data dianalisis dengan uji Mann Whitney dan diolah dengan SPSS. Hasil penelitian memperlihatkan pada minggu ke-2, tidak terdapat perbedaan bermakna reaksi inflamasi (P = 0,119), tulang imatur (P = 0,094), dan tulang matur (P = 0,130) diantara ketiga perlakuan. Pada minggu ke-4, tulang matur yang terbentuk lebih banyak pada perlakuan plasma kaya trombosit dan karbonat hidroksiapatit (P = 0,009). Simpulan: Pemberian plasma kaya trombosit dan karbonat hidroksiapatit dapat meningkatkan proses penutupan defek tulang kepala hewan percobaan tikus.Kata kunci : plasma kaya trombosit, karbonat hidroksiapatit, defek tulang kepala.

Angiogenetic transcriptional profiling reveals potential targets modulated in blood of patients with cardiovascular disorders

Vascular ◽  
2021 ◽  
pp. 170853812110523
Author(s):  
Joerg Ukkat ◽  
Artur Rebelo ◽  
Bogusz Trojanowicz
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Pathological Condition ◽  
Transcriptional Profiling ◽  
Platelet Derived Growth Factor ◽  
Vascular Pathology ◽  
Cardiovascular Disorders ◽  
Factor Alpha

Objectives Based on the angiogenetic, transcriptional profile of non-diseased and arteriosclerotic vessels, we aim to identify the leucocytic markers as a potential, minimal invasive tool supporting diagnosis of vascular pathology. Methods Transcriptional profiling was performed with Angiogenesis RT2 Profiler PCR (Polymerase Chain Reaction) array on three non-pathological and three arteriosclerotic vessels, followed by immunohistochemical staining. Based on these screening results, selected transcripts were employed for qPCR with specific primers and investigated on the blood RNA (RiboNucleic Acid) obtained from nine healthy controls and 29 patients with cardiovascular disorders. Thereafter, expression of these transcripts was investigated in vitro in human monocytes under calcification-mimicking conditions. Results and Conclusions Transcriptional profiling on the vessels revealed that out of 84 targets investigated two were up-regulated more than 100-fold, 18 more than 30 and 15 more than 10, while the most noticeable down-regulation was observed by ephrin-A3 and platelet-derived growth factor alpha (PDGFA) genes. Based on the vessel results, investigations of the selected blood transcripts revealed that thrombospondin 1 (THBS1), thrombospondin 3 (THBS3), transforming growth factor, beta receptor 1 (TGFBR1), platelet-derived growth factor alpha, plasminogen activator, urokinase (PLAU) and platelet/endothelial cell adhesion molecule 1 (PECAM-1) were significantly elevated in cardiovascular blood as compared to corresponding controls. Induction of calcification-related conditions in vitro to human THP-1 monocytes led to noticeable modulation of these transcripts. Taken together, these data demonstrate that leucocytic THBS1, THBS3, TGFBR1, platelet-derived growth factor alpha, PLAU and PECAM-1 have a correlation with cardiovascular disorders and could be used as a supportive tool predicting development of this pathological condition.

The John F. Maher Recipient Lecture 2004: Rage in the Peritoneum

2005 ◽  
Vol 25 (1) ◽  
pp. 8-11 ◽  
Author(s):  
An S. De Vriese
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Degradation Products ◽  
Mesothelial Cells ◽  
Cell Surface Receptor ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition

Several conditions in the peritoneal membrane of peritoneal dialysis (PD) patients promote the accumulation of advanced glycation end-products (AGEs), that is, the uremic state, exposure to high glucose concentrations, and exposure to glucose degradation products (GDPs). AGEs exert some of their biologic actions through binding with a cell surface receptor, termed RAGE. Interaction of AGEs with RAGE induces sustained cellular activation, including the production of the fibrogenic growth factor, transforming growth factor-beta (TGF-β). TGF-β is pivotal in the process of epithelial-to-mesenchymal transition, through which cells of epithelial origin acquire myofibroblastic characteristics. Myofibroblasts are involved in virtually all conditions of pathological fibrosis. Submesothelial fibrosis is an important feature in peritoneal biopsies of PD patients, especially of those with clinical problems. We therefore examined the role of RAGE in peritoneal fibrosis, in an animal model of uremia, of high glucose exposure, and of peritoneal dialysate exposure. All three models were characterized by accumulation of AGEs, upregulation of RAGE, and fibrosis. Antagonism of RAGE prevented the upregulation of TGF-β and fibrosis in the peritoneal membrane. We further examined the underlying mechanism of peritoneal fibrosis in the uremic model. Prominent myofibroblast transdifferentiation of mesothelial cells was identified by co-localization of cytokeratin and α-smooth muscle actin in submesothelial and interstitial fibrotic tissue. Antagonism of RAGE prevented conversion of mesothelial cells to myofibroblasts in uremia. In conclusion, we hypothesize that accumulation of AGEs in the peritoneal membrane, as a consequence of the uremic environment, chronic exposure to high glucose, and exposure to GDPs, results in an increased expression of RAGE. The interaction of AGEs with RAGE induces peritoneal fibrosis by virtue of upregulation of TGF-β and subsequent conversion of mesothelial cells into myofibroblasts.

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