PMID- 22595285 OWN - NLM STAT- MEDLINE DCOM- 20130610 LR - 20211203 IS - 1618-1298 (Electronic) IS - 0171-9335 (Linking) VI - 91 IP - 9 DP - 2012 Sep TI - Tumor necrosis factor-alpha (TNF-alpha)-mediated in vitro human retinal pigment epithelial (RPE) cell migration mainly requires Akt/mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2) signaling. PG - 728-37 LID - 10.1016/j.ejcb.2012.03.008 [doi] AB - When rhegmatogenous retinal detachment occurs, tumor necrosis factor-alpha (TNF-alpha) among other cytokines leaks into the subretinal space, induces resident retinal pigment epithelial (RPE) cells to migrate, which is the initial step of proliferative vitreoretinopathy (PVR). In the current study, we aim to understand how this is regulated by focusing the cellular mechanisms involved. Here we identified an Akt/Tuberous sclerosis protein 2 (TSC2)/mTOR complex1 (mTORC1) signaling pathway after TNF-alpha treatment to mediate RPE cell migration. Suppression of mTORC1 activation, either by its inhibitor rapamycin, or by activation of its suppressor AMP activated protein kinase (AMPK), inhibited TNF-alpha-mediated RPE cell migration, while RNA interference (RNAi)-mediated knocking-down of SIN1 or Rictor, two key components of mTOR complex 2 (mTORC2), had no significant effect on TNF-alpha-induced RPE cell migration. Our data provide initial evidence that TNF-alpha-mediated in vitro RPE cell migration mainly requires Akt/mTORC1, but not mTORC2 signaling. The results of this study may lead to indentify novel signaling targets against PVR. CI - Copyright (c) 2012 Elsevier GmbH. All rights reserved. FAU - Liu, Yuan AU - Liu Y AD - The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Cao, Guo-Fan AU - Cao GF FAU - Xue, Jinsong AU - Xue J FAU - Wan, Jerry AU - Wan J FAU - Wan, Yinsheng AU - Wan Y FAU - Jiang, Qing AU - Jiang Q FAU - Yao, Jin AU - Yao J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120516 PL - Germany TA - Eur J Cell Biol JT - European journal of cell biology JID - 7906240 RN - 0 (Multiprotein Complexes) RN - 0 (Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Cell Line MH - *Cell Movement MH - Humans MH - Mechanistic Target of Rapamycin Complex 1 MH - Mechanistic Target of Rapamycin Complex 2 MH - Multiprotein Complexes/metabolism MH - Proteins/*metabolism MH - Retinal Pigment Epithelium/*cytology/*metabolism MH - *Signal Transduction MH - TOR Serine-Threonine Kinases/metabolism MH - Tumor Necrosis Factor-alpha/*metabolism EDAT- 2012/05/19 06:00 MHDA- 2013/06/12 06:00 CRDT- 2012/05/19 06:00 PHST- 2011/12/19 00:00 [received] PHST- 2012/03/24 00:00 [revised] PHST- 2012/03/26 00:00 [accepted] PHST- 2012/05/19 06:00 [entrez] PHST- 2012/05/19 06:00 [pubmed] PHST- 2013/06/12 06:00 [medline] AID - S0171-9335(12)00061-1 [pii] AID - 10.1016/j.ejcb.2012.03.008 [doi] PST - ppublish SO - Eur J Cell Biol. 2012 Sep;91(9):728-37. doi: 10.1016/j.ejcb.2012.03.008. Epub 2012 May 16.