Platelet-derived growth factor-D induces expression of cyclooxygenase-2 in rat mesangial cells through activation of PI3K/PKB and PKCs

  • Authors:
    • Yu-Kyoung Park
    • Byeong-Churl Jang
    • Misun Choi
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  • Published online on: December 18, 2012     https://doi.org/10.3892/ijmm.2012.1216
  • Pages: 447-452
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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.
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February 2013
Volume 31 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Park Y, Jang B and Choi M: Platelet-derived growth factor-D induces expression of cyclooxygenase-2 in rat mesangial cells through activation of PI3K/PKB and PKCs. Int J Mol Med 31: 447-452, 2013
APA
Park, Y., Jang, B., & Choi, M. (2013). Platelet-derived growth factor-D induces expression of cyclooxygenase-2 in rat mesangial cells through activation of PI3K/PKB and PKCs. International Journal of Molecular Medicine, 31, 447-452. https://doi.org/10.3892/ijmm.2012.1216
MLA
Park, Y., Jang, B., Choi, M."Platelet-derived growth factor-D induces expression of cyclooxygenase-2 in rat mesangial cells through activation of PI3K/PKB and PKCs". International Journal of Molecular Medicine 31.2 (2013): 447-452.
Chicago
Park, Y., Jang, B., Choi, M."Platelet-derived growth factor-D induces expression of cyclooxygenase-2 in rat mesangial cells through activation of PI3K/PKB and PKCs". International Journal of Molecular Medicine 31, no. 2 (2013): 447-452. https://doi.org/10.3892/ijmm.2012.1216