PMID- 22820188 OWN - NLM STAT- MEDLINE DCOM- 20130221 LR - 20211203 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 425 IP - 1 DP - 2012 Aug 17 TI - TNF-alpha promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling. PG - 33-8 LID - 10.1016/j.bbrc.2012.07.044 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-alpha promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-alpha-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-alpha-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-alpha promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Wang, Cheng-hu AU - Wang CH AD - The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China. FAU - Cao, Guo-Fan AU - Cao GF FAU - Jiang, Qin AU - Jiang Q FAU - Yao, Jin AU - Yao J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120720 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (MAPKAP1 protein, human) 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 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Adaptor Proteins, Signal Transducing/genetics/metabolism MH - Cell Movement/*drug effects/physiology MH - Cells, Cultured MH - Humans MH - Matrix Metalloproteinase 9/*biosynthesis MH - Mechanistic Target of Rapamycin Complex 1 MH - Multiprotein Complexes MH - Pigment Epithelium of Eye/*drug effects/enzymology/physiology MH - Proteins/*metabolism MH - Proto-Oncogene Proteins c-akt/*biosynthesis MH - RNA Interference MH - Signal Transduction MH - TOR Serine-Threonine Kinases/genetics/metabolism MH - Tumor Necrosis Factor-alpha/*pharmacology MH - Vitreoretinopathy, Proliferative/enzymology/pathology EDAT- 2012/07/24 06:00 MHDA- 2013/02/22 06:00 CRDT- 2012/07/24 06:00 PHST- 2012/06/13 00:00 [received] PHST- 2012/07/11 00:00 [accepted] PHST- 2012/07/24 06:00 [entrez] PHST- 2012/07/24 06:00 [pubmed] PHST- 2013/02/22 06:00 [medline] AID - S0006-291X(12)01340-X [pii] AID - 10.1016/j.bbrc.2012.07.044 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2012 Aug 17;425(1):33-8. doi: 10.1016/j.bbrc.2012.07.044. Epub 2012 Jul 20.