title: Platelet-derived growth factor-D induces expression of cyclooxygenase-2             in rat mesangial cells through activation of PI3K/PKB and PKCs.
abstract: Platelet-derived growth factor (PDGF)-D is suggested to be a key factor             in the development of several renal pathologies, including mesangioproliferative             glomerulonephritis. Cyclooxygenase (COX)-2 is a protein involved in the biosynthesis             of inflammatory prostaglandins. In this study, we investigated the effect of PDGF-D             on the regulation of COX-2 expression in rat mesangial cells (RMCs). Treatment             with PDGF-D induced COX-2 at both the protein and mRNA levels in RMCs, suggesting             that the PDGF-D-mediated induction of COX-2 is due to COX-2 transcriptional upregulation.             PDGF-D treatment also led to a rapid but transient activation of PKB and extracellular             signal regulated kinase (ERK)-1/2. Activities of JNK-1/2 and p38 MAPK, however,             were not influenced by PDGF-D in RMCs. Markedly, pharmacological inhibition studies             showed that pretreatment with LY294002 (a PI3K/PKB inhibitor) or GF109203X (a             pan-PKC inhibitor) suppressed the PDGF-D-induced expression of COX-2 protein and             mRNA, while pretreatment with PD98059 (an ERK-1/2 inhibitor) or PP1 (an Src inhibitor)             had no effect on it. These findings collectively demonstrate for the first time             that PDGF-D induces COX-2 by transcriptional upregulation in RMCs and the induction             is largely related to PI3K/PKB and PKCs activities.
authors.affiliation: Department of Medical Genetic Engineering, School of Medicine,                     Keimyung University, Dalseo-gu, Daegu 704-701, Republic of Korea.
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Park
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.forename: Misun
authors.initials: M
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D008222:Lymphokines / Q000378:metabolism*; D050527:Mesangial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D015533:Transcriptional Activation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051546:Cyclooxygenase 2; D008222:Lymphokines; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019869:Phosphatidylinositol 3-Kinases; D010982:Platelet-Derived Growth Factor; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; C498952:Pdgfd protein, rat