title: Mesenchymal marker expression is elevated in Müller cells exposed to high glucose and in animal models of diabetic retinopathy.
abstract: Müller cells are retinal glial cells and exhibit a fibroblast-like phenotype and ability to migrate in diabetic retinopathy (DR). However, expression of mesenchymal markers, which promote fibrosis in various organs, has not been characterized in the diabetic retina. We examined changes in the expression of these markers in Müller cells exposed to high glucose and in animal models of diabetic retinopathy. High glucose conditions increased mesenchymal maker expression and migration in Müller cells. Snail, N-cadherin, Vimentin, β-catenin, and α-smooth muscle actin (α-SMA) levels were all dramatically increased in retinas from humans with diabetic retinopathy (DR) and from DR mouse models. In addition, Snail overexpression increased the expression of connective tissue growth factor (CTGF) and fibronectin, while Snail knockdown attenuated high glucose-induced increases in fibronectin and CTGF expression. These results demonstrate for the first time that mesenchymal markers are upregulated in retinas from a diabetic mouse model, and that Snail and N-cadherin levels are also increased in Müller cells exposed to high glucose. This suggests mesenchymal proteins may play a crucial role in the development of DR.
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ti
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Di
authors.initials: D
authors.lastname: Che
authors.affiliation: Department of Ophthalmology, Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jinye
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Ophthalmology, Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: HaiJun
authors.initials: H
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: ChaoYang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Hong
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Caiqi
authors.initials: C
authors.lastname: Ma
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zhonghan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Guangdong Engineering and Technology Research Center for Disease-Model Animals, Sun Yat-Sen University, Guangzhou, China.
authors.forename: WeiBin
authors.initials: W
authors.lastname: Cai
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Physiology, University of Oklahoma, Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Jianxing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Key Laboratory of Functional Molecules from Marine Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.affiliation: Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|China Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Gao
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D063928:Ependymoglial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D013311:Streptozocin; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015415:Biomarkers; C495270:CTNNB1 protein, human; D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014746:Vimentin; D051176:beta Catenin; D013311:Streptozocin; D005947:Glucose
keywords: diabetic retinopathy; hyperglycemia; mesenchymal markers; müller cells