title: Sprouty2 Suppresses Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells through Blockade of Smad2 and ERK1/2 Pathways.
abstract: Transforming growth factor β (TGFβ)-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) plays a key role in the pathogenesis of anterior subcapsular cataract (ASC) and capsule opacification. In mouse lens, Sprouty2 (Spry2) has a negative regulatory role on TGFβ signaling. However, the regulation of Spry2 during ASC development and how Spry2 modulates TGFβ signaling pathway in human LECs have not been characterized. Here, we demonstrate that Spry2 expression level is decreased in anterior capsule LECs of ASC patients. Spry2 negatively regulates TGFβ2-induced EMT and migration of LECs through inhibition of Smad2 and ERK1/2 phosphorylation. Also, blockade of Smad2 or ERK1/2 activation suppresses EMT caused by Spry2 downregulation. Collectively, our results for the first time show in human LECs that Spry2 has an inhibitory role in TGFβ signaling pathway. Our findings in human lens tissue and epithelial cells suggest that Spry2 may become a novel therapeutic target for the prevention and treatment of ASC and capsule opacification.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xuhua
authors.initials: X
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Haotian
authors.initials: H
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Weirong
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D015153:Blotting, Western; D002386:Cataract / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D051899:Smad2 Protein / Q000037:antagonists & inhibitors* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497782:SMAD2 protein, human; C485561:SPRY2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta