期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 61, 期 8, 页码 -出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.61.8.34
关键词
epiretinal membranes; macular puckers; MIO-M1 cells; HSP90; TGF-beta
资金
- MIUR (Ministero dell'Istruzione, dell'Universita e della Ricerca) Grant Dipartimento di eccellenza 2018-2022
- I.Ri.Fo.R Onlus (Institute for the Research, Formation and Rehabilitation) Italian Union of Blind and Visually Impaired People
PURPOSE. This work was aimed to further characterize cells of idiopathic epiretinal membranes (iERMs). We wanted to determine the contribution of 90-kDa heat shock protein (HSP90) to sustain the transforming growth factor-beta (TGF-beta)-mediated signal transduction pathway in iERM. METHODS. Immunofluorescence and confocal microscopy were carried out on deplasticized sections from 36 epiretinal membranes processed for electron microscopy and on frozen sections from five additional samples with antibodies against alpha-smooth muscle actin (alpha SMA), vimentin, glial fibrillary acidic protein (GFAP), SMAD2, HSP90 alpha, type-II TGF-beta 1 receptor (T beta RII), type-I collagen, and type-IV collagen. In addition, Muller MIO-M1 cells were transfected with HSP90 and challenged with TGF-beta 1. RESULTS. Double and triple labeling experiments showed that a variable number of T beta RII+ cells were present in 94.1% of tested iERMs and they were mostly GFAP(-)/alpha SMA(+)/vimentin(+)/HSP90 alpha(+). In almost half of the cases these cells contained type-I collagen, suggesting their involvement in matrix deposition. HSP90 overexpressing MIO-M1 cells challenged with TGF-beta 1 showed increased levels of T beta RII, SMAD2, SMAD3, and phosphor-SMAD2. Nuclear SMAD2 staining could be observed in HSP90 alpha(+) cells on frozen sections of iERMs. CONCLUSIONS. Cells in iERMs that express T beta RII are also HSP90 alpha(+) and show the antigenic profile of myofibroblast-like cells as they are GFAP-/alpha SMA(+)/vimentin(+). HSP90 alpha-overexpressing MIO-M1 cells challenged with TGF-beta 1 showed an increased activation of the SMAD pathway implying that HSP90 alpha might play a role in sustaining the TGF-beta 1-induced fibrotic response of iERM cells.
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