Interaction of MAPK and 12-lipoxygenase pathways in growth and matrix protein expression in mesangial cells

Marpadga A. Reddy, Sharon G. Adler, Young Sook Kim, Linda Lanting, John Rossi, Shin Wook Kang, Jerry L. Nadler, Asha Shahed, Rama Natarajan

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Abstract

The lipoxygenase (LO) pathway of arachidonate metabolism and mitogen-activated protein kinases (MAPKs) can mediate cellular growth and ANG II effects in vascular smooth muscle cells. However, their role in renal mesangial cells (MC) is not very clear. ANG II treatment of rat MC significantly increased 12-LO mRNA expression and formation of the 12-LO product 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE; P << 0.03] ANG II-induced [ 3H]leucine incorporation was blocked by an LO inhibitor, cinnamyl-3-4-dihydroxy-α-cyanocinnamate (P < 0.02). 12(S)-HETE and ANG II directly induced cellular hypertrophy and fibronectin (FN) expression (P < 0.01) to a similar extent. ANG II and 12(S)-HETE led to activation of p38 MAPK and its target transcription factor cAMP-responsive element-binding protein (CREB). ANG II and 12(S)-HETE-induced CREB activation and [ 3H]leucine incorporation were blocked by the p38 MAPK inhibitor SB-202190. A specific molecular inhibitor of rat 12-LO mRNA, namely, a novel ribozyme, could attenuate ANG II-induced FN mRNA. Thus p38 MAPK-dependent CREB activation may mediate ANG II- and LO product-induced FN expression and cellular growth in rat MC. ANG II effects may be mediated by the LO pathway. These results suggest a novel interaction between LO and p38 MAPK activation in MC matrix synthesis associated with renal complications.

Original languageEnglish
Pages (from-to)F985-F994
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number5 52-5
Publication statusPublished - 2002 Nov 1

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Reddy, M. A., Adler, S. G., Kim, Y. S., Lanting, L., Rossi, J., Kang, S. W., Nadler, J. L., Shahed, A., & Natarajan, R. (2002). Interaction of MAPK and 12-lipoxygenase pathways in growth and matrix protein expression in mesangial cells. American Journal of Physiology - Renal Physiology, 283(5 52-5), F985-F994.