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

Research output: Contribution to journalArticle

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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
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number5 52-5
Publication statusPublished - 2002 Nov 1

Fingerprint

Mitogen-Activated Protein Kinase 12
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Arachidonate 12-Lipoxygenase
Mesangial Cells
p38 Mitogen-Activated Protein Kinases
Lipoxygenase
Fibronectins
Growth
Lipoxygenase Inhibitors
Carrier Proteins
Proteins
Leucine
Messenger RNA
Arachidonate Lipoxygenases
Catalytic RNA
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Vascular Smooth Muscle
Hypertrophy
Smooth Muscle Myocytes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

Cite this

Reddy, Marpadga A. ; Adler, Sharon G. ; Kim, Young Sook ; Lanting, Linda ; Rossi, John ; Kang, Shin-Wook ; Nadler, Jerry L. ; Shahed, Asha ; Natarajan, Rama. / Interaction of MAPK and 12-lipoxygenase pathways in growth and matrix protein expression in mesangial cells. In: American Journal of Physiology - Renal Physiology. 2002 ; Vol. 283, No. 5 52-5.
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title = "Interaction of MAPK and 12-lipoxygenase pathways in growth and matrix protein expression in mesangial cells",
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.",
author = "Reddy, {Marpadga A.} and Adler, {Sharon G.} and Kim, {Young Sook} and Linda Lanting and John Rossi and Shin-Wook Kang and Nadler, {Jerry L.} and Asha Shahed and Rama Natarajan",
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month = "11",
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Reddy, MA, Adler, SG, Kim, YS, Lanting, L, Rossi, J, Kang, S-W, Nadler, JL, 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, vol. 283, no. 5 52-5.

Interaction of MAPK and 12-lipoxygenase pathways in growth and matrix protein expression in mesangial cells. / Reddy, Marpadga A.; Adler, Sharon G.; Kim, Young Sook; Lanting, Linda; Rossi, John; Kang, Shin-Wook; Nadler, Jerry L.; Shahed, Asha; Natarajan, Rama.

In: American Journal of Physiology - Renal Physiology, Vol. 283, No. 5 52-5, 01.11.2002.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interaction of MAPK and 12-lipoxygenase pathways in growth and matrix protein expression in mesangial cells

AU - Reddy, Marpadga A.

AU - Adler, Sharon G.

AU - Kim, Young Sook

AU - Lanting, Linda

AU - Rossi, John

AU - Kang, Shin-Wook

AU - Nadler, Jerry L.

AU - Shahed, Asha

AU - Natarajan, Rama

PY - 2002/11/1

Y1 - 2002/11/1

N2 - 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.

AB - 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.

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