{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:23:29Z","timestamp":1790519009975,"version":"4.1.0"},"reference-count":31,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T00:00:00Z","timestamp":1355788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T00:00:00Z","timestamp":1355788800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Vasc Res"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>Tumor necrosis factor (TNF)-\u03b1 can alter tissue repair functions in a variety of cells including endothelial cells. However, the mechanism by which TNF-\u03b1 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-\u03b1 on the tissue repair functions of human pulmonary artery endothelial cells (HPAECs). TNF-\u03b1 protected HPAECs from undergoing apoptosis induced by serum and growth factor deprivation, augmented collagen gel contraction, and stimulated wound closure. TNF-\u03b1 activated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1\/2), and p38. Inhibitors of JNK (SP600125, 5 \u00b5&lt;smlcap&gt;m&lt;\/smlcap&gt;) or ERK1\/2 (PD98059, 5 \u00b5&lt;smlcap&gt;m&lt;\/smlcap&gt;) significantly inhibited TNF-\u03b1-stimulated cell survival, contraction of collagen gels, and wound closure. In contrast, the p38 inhibitor SB203580 (5 \u00b5&lt;smlcap&gt;m&lt;\/smlcap&gt;) further amplified all of the TNF-\u03b1 effects on HPAECs. TNF-\u03b1 specifically activated p38\u03b1 but not other p38 isoforms and suppression of p38\u03b1 by an siRNA resulted in further amplification of the TNF-\u03b1 effect. These results suggest that TNF-\u03b1 stimulates tissue repair functions of HPAECs, and this may be mediated, at least in part, positively via JNK and ERK1\/2, and negatively through p38\u03b1. MAPKs may play a role in endothelial cell-mediated tissue repair, especially in an inflammatory milieu where TNF-\u03b1 is present.<\/jats:p>","DOI":"10.1159\/000345525","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T08:18:49Z","timestamp":1355818729000},"page":"145-156","source":"Crossref","is-referenced-by-count":17,"title":["Differential Roles of JNK, ERK1\/2, and p38 Mitogen-Activated Protein Kinases on Endothelial Cell Tissue Repair Functions in Response to Tumor Necrosis 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