Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Activated coagulation factor X: A novel mitogenic stimulus for human mesangial cells
Autore:
Monno, R; Grandaliano, G; Faccio, R; Ranieri, E; Martino, C; Gesualdo, L; Schena, FP;
Indirizzi:
Univ Bari, Dept Emergency & Transplantat, Div Nephrol, Bari, Italy Univ Bari Bari Italy Emergency & Transplantat, Div Nephrol, Bari, Italy Univ Bari, Inst Human Anat, Bari, Italy Univ Bari Bari ItalyUniv Bari, Inst Human Anat, Bari, Italy
Titolo Testata:
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
fascicolo: 5, volume: 12, anno: 2001,
pagine: 891 - 899
SICI:
1046-6673(200105)12:5<891:ACFXAN>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; PROTEIN-TYROSINE PHOSPHORYLATION; GROWTH-FACTOR; MOLECULAR-CLONING; THROMBIN-RECEPTOR; PDGF EXPRESSION; HUMAN-KIDNEY; KINASE; PROLIFERATION; PATHWAYS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Schena, FP Univ Bari Policlin, Dept Emergency & Transplantat, Piazza Giulio Cesare 11, I-70124 Bari, Italy Univ Bari Policlin Piazza Giulio Cesare 11Bari Italy I-70124
Citazione:
R. Monno et al., "Activated coagulation factor X: A novel mitogenic stimulus for human mesangial cells", J AM S NEPH, 12(5), 2001, pp. 891-899

Abstract

Intraglomerular activation of the coagulation cascade is a common feature of mesangioproliferative glomerulonephritis. Besides thrombin, very little is known about the cellular effects of other components of the coagulation system. This study investigated the effect of activated factor X (FXa) on cultured human mesangial cells. This serine protease induced a significant and dose-dependent increase in DNA synthesis. In addition to its mitogenic effect, FXa caused a striking upregulation of platelet-derived growth factor(PDGF) A and B chain gene expression. Next, the intracellular mitogenic signaling pathways activated by FXa were investigated. FXa induced a rapid spike in cytosolic calcium concentration followed by a sustained plateau. This response was not influenced by the downregulation of thrombin receptors. In addition, FXa stimulated a significant upregulation of different tyrosine-phosphorylated proteins. One of these phosphorylated cellular proteins was represented by the c-jun N-terminal kinase, a member of the mitogen-activated protein kinase family. To evaluate the role of FXa enzymatic activity and of PDGF autocrine secretion, FXa-induced DNA synthesis was studied in the presence of leupeptin, a specific serine protease inhibitor, and neutralizing anti-PDGF antibody. To investigate the role of tyrosine kinase (TK) activation on FXa mitogenic effect, FXa-stimulated thymidine uptake was evaluated in the presence of genistein and herbimycin A, two powerful and specific TK inhibitors. FXa-elicited DNA synthesis was also examined after protein kinase C (PKC) downregulation by prolonged incubation with phorbol-12-myristate-13-acetate to study the influence of the phospholipase C-PKC axis. The proliferative effect of FXa required its proteolytic activity, and the activation of TK was only partially dependent on PKC activation while it was PDGF independent. Finally, it was shown by reverse transcription-PCR thatmesangial cells do not express the signaling splicing variant of the putative FXa receptor, effector protease receptor-1. In conclusion, the present study demonstrated that FXa is a powerful mitogenic factor for human mesangial cells, and it induces its cellular effect not through effector proteasereceptor-1, but most likely by binding a protease-activated receptor and activating phospholipase C-PKC and TK signaling pathways.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 06:25:11