Dipyridamole inhibits cobalt chloride-induced osteopontin expression in NRK52E cells

Tso Hsiao Chen, Chia Fang Chang, Shu Chuan Yu, Jiueng Chueng Wang, Cheng Hsien Chen, Paul Chan, Horng Mo Lee

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Osteopontin plays a pivotal role in the progression of interstitial fibrosis in renal ischemia. In the present study, rat renal tubular NRK52E cells treated with hypoxia mimetic cobalt chloride (CoCl2) increased osteopontin production, and are associated with increased phosphorylation of Akt/PKB (protein kinase B) and p38 mitogen-activated protein kinase (p38MAPK). Furthermore, pretreatment of cells with l-N-acetylcysteine (an antioxidant) inhibited CoCl2-stimulated osteopontin protein expression and p38MAPK phosphorylation, but not Akt/PKB phosphorylation. Pretreatment of cells with anti-inflammatory agents celecoxib, tanshinone IIA, and dipyridamole inhibited CoCl2-induced osteopontin production paralleled by heme oxygenase-1 (HO-1) induction. Pretreatment of cells with tin protoporphyrin (a HO-1 inhibitor) or hemoglobin (a carbon monoxide scavenging agent) reversed dipyridamole inhibition of osteopontin expression. Moreover, transfection of HO-1 small interfering RNA (siRNA) reduced dipyridamole-stimulated mitogen-activated protein kinase phosphatase-1 (MKP-1) phosphorylation. Conversely, MKP-1 knockdown reversed dipyridamole inhibition of osteopontin expression. Taken together, these data suggest that dipyridamole may inhibit CoCl2-induced osteopontin expression through HO-1 induction. Increased HO-1 may catalyze the conversion of heme into carbon monoxide, in turn carbon monoxide activates MKP-1. MKP-1 activation inhibits the p38MAPK signaling pathway that mediates CoCl2-induced osteopontin production.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number1-3
Publication statusPublished - Jun 24 2009


  • Dipyridamole
  • Heme oxygenase-1
  • NRK52E tubular cell
  • Osteopontin

ASJC Scopus subject areas

  • Pharmacology


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