title: TNF-α promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling.
abstract: Tumor necrosis factor-alpha (TNF-α) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-α 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-α-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-α-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-α promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.
authors: The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Cheng-hu
authors: CH
authors: Wang
authors: Guo-Fan
authors: GF
authors: Cao
authors: Qin
authors: Q
authors: Jiang
authors: Jin
authors: J
authors: Yao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D034622:RNA Interference; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D018630:Vitreoretinopathy, Proliferative / Q000201:enzymology / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493277:MAPKAP1 protein, human; D046912:Multiprotein Complexes; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020780:Matrix Metalloproteinase 9