Journal article
Epo inhibits the fibrosis and migration of Muller glial cells induced by TGF-beta and high glucose
Graefe's archive for clinical and experimental ophthalmology, Vol.254(5), pp.881-890
01 May 2016
PMID: 26907931
Abstract
Background In proliferative diabetic retinopathy (PDR), Muller glial cells (MGCs) acquire migratory ability and exhibit a fibroblast-like phenotype. These activated MGCs contribute to the formation of epiretinal membrane, which will stretch the retina, and cause retinal detachment and vitreous hemorrhage. Erythropoietin (Epo) is now found effective in ameliorating renal fibrosis by inhibiting epithelial-to-mesenchymal transition of tubular epithelial cells. This study is undertaken to determine whether Epo has an effect in inhibiting MGCs activation to attenuate epiretinal membrane formation in PDR.
Method MIO-M1 cell line was used in this study. As a pilot test to determine the most efficient treatment time and concentration of Epo, levels of connective tissue growth factor (CTGF) and transforming growth factor-beta (TGF-beta) were measured by real-time PCR, after treatment with Epo on MGCs cultured in high glucose. MGCs were cultured in high glucose and normal glucose for 2 days, with or without TGF-beta as a pro-fibrogenic cytokine. Epo was introduced at the same time. Immunofluorescence targeting alpha-smooth muscle actin (alpha-SMA), fibronectin, and glial fibrillary acidic protein (GFAP) was performed to explore the cell phenotype. Matrix metalloproteinase 9 (MMP9) mRNA level was detected by real-time PCR. Protein levels of CTGF and cytoskeletal proteins like alpha-SMA and fibronectin were measured by enzyme-linked immunosorbent assay (ELISA) and Western blot respectively. Wound-healing assay was applied to evaluate the migratory ability of MGCs, and actin-tracker green was used to draw the structure of F-actin in MGCs.
Results After being seeded into high-glucose medium containing TGF-beta, MGCs expressed a larger amount of MMP9 mRNA as well as alpha-SMA, fibronectin at protein level. They secreted more CTGF, and their F-actin reorganized in a parallel manner and showed a stronger ability to migrate. In addition, these changes, including mRNA and protein expression, F-actin assembling, and cell migration, could be attenuated significantly by Epo treatment.
Conclusion High glucose together with TGF-beta promote MGCs to exhibit a fibroblast-like phenotype and develop a greater migratory ability. These changes can be inhibited by Epo, which therefore may contribute to the controlling of epiretinal membrane formation.
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Details
- Title
- Epo inhibits the fibrosis and migration of Muller glial cells induced by TGF-beta and high glucose
- Creators
- Wentao Luo - Shanghai Tenth People's HospitalLiumei Hu - Shanghai Tenth People's HospitalWeiye Li - Drexel UniversityGuotong Xu - Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Ophthalmol, Shanghai 200092, Peoples R ChinaLinxinyu Xu - Shanghai Tenth People's HospitalConghui Zhang - Shanghai Tenth People's HospitalFang Wang - Shanghai Tenth People's Hospital
- Publication Details
- Graefe's archive for clinical and experimental ophthalmology, Vol.254(5), pp.881-890
- Publisher
- Springer Nature
- Number of pages
- 10
- Grant note
- 81200693 / National Nature Science Foundation of China; National Natural Science Foundation of China (NSFC)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Ophthalmology [Historical]
- Identifiers
- 991019167637904721
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- Domestic collaboration
- International collaboration
- Web of Science research areas
- Ophthalmology