Role of macrophage migration inhibitory factor (MIF) in the effects of oxidative stress on human retinal pigment epithelial cells

Proliferative vitreoretinopathy (PVR) is the major cause of treatment failure in individuals who undergo surgery for retinal detachment. The epithelial‐mesenchymal transition (EMT) in retinal pigment epithelium (RPE) cells contributes to the pathogenesis of PVR. Oxidative stress is thought to play a role in the progression of retinal diseases including PVR. We have now examined the effects of oxidative stress on the EMT and related processes in the human RPE cell line. We found that H2O2 induced the contraction of RPE cells in a three‐dimensional collagen gel. Analysis of a cytokine array revealed that H2O2 specifically increased the release of macrophage migration inhibitory factor (MIF) from RPE cells. Reverse transcription–polymerase chain reaction and immunoblot analyses showed that H2O2 increased the expression of MIF in RPE cells. Immunoblot and immunofluorescence analyses revealed that H2O2 upregulated the expression of α–SMA and vimentin and downregulated that of ZO‐1 and N‐cadherin. Consistent with these observations, the transepithelial electrical resistance of cell was reduced by exposure to H2O2. The effects of oxidative stress on EMT‐related and junctional protein expression as well as on transepithelial electrical resistance were inhibited by antibodies to MIF, but they were not mimicked by treatment with recombinant MIF. Finally, analysis with a profiling array for mitogen‐activated protein kinase signalling revealed that H2O2 specifically indu...

Source: Cell Biochemistry and Function - August 1, 2017 Category: Biochemistry Authors: Ji ‐Ae Ko, Yasuyuki Sotani, Diah Gemala Ibrahim, Yoshiaki Kiuchi Tags: RESEARCH ARTICLE Source Type: research