title: Tumor necrosis factor-alpha (TNF-α)-mediated in vitro human retinal pigment epithelial (RPE) cell migration mainly requires Akt/mTOR complex 1 (mTORC1), but not mTOR complex 2 (mTORC2) signaling.
abstract: When rhegmatogenous retinal detachment occurs, tumor necrosis factor-alpha (TNF-α) 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-α 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-α-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-α-induced RPE cell migration. Our data provide initial evidence that TNF-α-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.
authors.affiliation: The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Guo-Fan
authors.initials: GF
authors.lastname: Cao
authors.forename: Jinsong
authors.initials: J
authors.lastname: Xue
authors.forename: Jerry
authors.initials: J
authors.lastname: Wan
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wan
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases