Differential roles of JNK, ERK1/2, and p38 mitogen-activated protein kinases on endothelial cell tissue repair functions in response to tumor necrosis factor-α

Nobuhiro Kanaji, Amy Nelson, Xingqi Wang, Tadashi Sato, Masanori Nakanishi, Yoko Gunji, Hesham E Basma, Joel Michalski, Maha Farid, Stephen I. Rennard, Xiang-de Liu

Research output: Contribution to journalArticle

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Abstract

Tumor necrosis factor (TNF)-α can alter tissue repair functions in a variety of cells including endothelial cells. However, the mechanism by which TNF-α mediates these functional changes has not fully been studied. We investigated the role of mitogen-activated protein kinases (MAPKs) on mediating the regulatory effect of TNF-α on the tissue repair functions of human pulmonary artery endothelial cells (HPAECs). TNF-α protected HPAECs from undergoing apoptosis induced by serum and growth factor deprivation, augmented collagen gel contraction, and stimulated wound closure. TNF-α activated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38. Inhibitors of JNK (SP600125, 5 μm) or ERK1/2 (PD98059, 5 μm) significantly inhibited TNF-α-stimulated cell survival, contraction of collagen gels, and wound closure. In contrast, the p38 inhibitor SB203580 (5 μm) further amplified all of the TNF-α effects on HPAECs. TNF-α specifically activated p38α but not other p38 isoforms and suppression of p38α by an siRNA resulted in further amplification of the TNF-α effect. These results suggest that TNF-α stimulates tissue repair functions of HPAECs, and this may be mediated, at least in part, positively via JNK and ERK1/2, and negatively through p38α. MAPKs may play a role in endothelial cell-mediated tissue repair, especially in an inflammatory milieu where TNF-α is present.

Original languageEnglish (US)
Pages (from-to)145-156
Number of pages12
JournalJournal of Vascular Research
Volume50
Issue number2
DOIs
StatePublished - Feb 1 2013

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Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
Endothelium
Phosphotransferases
Endothelial Cells
Tumor Necrosis Factor-alpha
Pulmonary Artery
Mitogen-Activated Protein Kinases
Collagen
Gels
JNK Mitogen-Activated Protein Kinases
Wounds and Injuries
Small Interfering RNA
Cell Survival
Intercellular Signaling Peptides and Proteins
Protein Isoforms
Apoptosis

Keywords

  • Apoptosis
  • Endothelial cells
  • Mitogen-activated protein kinase
  • Wound repair

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Differential roles of JNK, ERK1/2, and p38 mitogen-activated protein kinases on endothelial cell tissue repair functions in response to tumor necrosis factor-α. / Kanaji, Nobuhiro; Nelson, Amy; Wang, Xingqi; Sato, Tadashi; Nakanishi, Masanori; Gunji, Yoko; Basma, Hesham E; Michalski, Joel; Farid, Maha; Rennard, Stephen I.; Liu, Xiang-de.

In: Journal of Vascular Research, Vol. 50, No. 2, 01.02.2013, p. 145-156.

Research output: Contribution to journalArticle

Kanaji, Nobuhiro ; Nelson, Amy ; Wang, Xingqi ; Sato, Tadashi ; Nakanishi, Masanori ; Gunji, Yoko ; Basma, Hesham E ; Michalski, Joel ; Farid, Maha ; Rennard, Stephen I. ; Liu, Xiang-de. / Differential roles of JNK, ERK1/2, and p38 mitogen-activated protein kinases on endothelial cell tissue repair functions in response to tumor necrosis factor-α. In: Journal of Vascular Research. 2013 ; Vol. 50, No. 2. pp. 145-156.
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