HMGB1 and Caveolin-1 related to RPE cell senescence in age-related macular degeneration.

HMGB1 and Caveolin-1 related to RPE cell senescence in age-related macular degeneration. Aging (Albany NY). 2019 Jul 07;: Authors: Sun S, Cai B, Li Y, Su W, Zhao X, Gong B, Li Z, Zhang X, Wu Y, Chen C, Tsang SH, Yang J, Li X Abstract Accumulation of lipofuscin in the retinal pigment epithelium (RPE) is considered a major cause of RPE dysfunction and senescence in age-related macular degeneration (AMD), and N-retinylidene-N-retinylethanolamine (A2E) is the main fluorophore identified in lipofuscin from aged human eyes. Here, human-induced pluripotent stem cell (iPSC)-RPE was generated from healthy individuals to reveal proteomic changes associated with A2E-related RPE cell senescence. A novel RPE cell senescence-related protein, high-mobility group box 1 (HMGB1), was identified based on proteomic mass spectrometry measurements on iPSC-RPE with A2E treatment. Furthermore, HMGB1 upregulated Caveolin-1, which also was related RPE cell senescence. To investigate whether changes in HMGB1 and Caveolin-1 expression under A2E exposure contribute to RPE cell senescence, human ARPE-19 cells were stimulated with A2E; expression of HMGB1, Caveolin-1, tight junction proteins and senescent phenotypes were verified. HMGB1 inhibition alleviated A2E induced cell senescence. Migration of RPE cells was evaluated. Notably, A2E less than or equal to 10μM induced both HMGB1 and Caveolin-1 protein upregulation and HMGB1 translocation, while Caveolin-1 expr...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research