Sprouty2 Suppresses Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells through Blockade of Smad2 and ERK1/2 Pathways

Xuhua Tan; Yi Zhu; Chuan Chen; Xiaoyun Chen; Yingyan Qin; Bo Qu; Lixia Luo; Haotian Lin; Mingxing Wu; Weirong Chen; Yizhi Liu

doi:10.1371/journal.pone.0159275

Sprouty2 Suppresses Epithelial-Mesenchymal Transition of Human Lens Epithelial Cells through Blockade of Smad2 and ERK1/2 Pathways

PLoS One. 2016 Jul 14;11(7):e0159275. doi: 10.1371/journal.pone.0159275. eCollection 2016.

Authors

Xuhua Tan¹, Yi Zhu¹, Chuan Chen¹, Xiaoyun Chen¹, Yingyan Qin¹, Bo Qu¹, Lixia Luo¹, Haotian Lin¹, Mingxing Wu¹, Weirong Chen¹, Yizhi Liu¹

Affiliation

¹ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.

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.

MeSH terms

Blotting, Western
Cataract / metabolism
Cells, Cultured
Down-Regulation
Epithelial Cells / metabolism*
Epithelial-Mesenchymal Transition / physiology*
Fluorescent Antibody Technique
Humans
Intracellular Signaling Peptides and Proteins / physiology*
Lens, Crystalline / cytology*
Lens, Crystalline / metabolism
MAP Kinase Signaling System / physiology*
Membrane Proteins / physiology*
Smad2 Protein / antagonists & inhibitors*
Smad2 Protein / physiology
Transforming Growth Factor beta / physiology

Substances

Intracellular Signaling Peptides and Proteins
Membrane Proteins
SMAD2 protein, human
SPRY2 protein, human
Smad2 Protein
Transforming Growth Factor beta

Grants and funding

This study was supported by the International Cooperation and Communication Project of the National Natural Science Foundation of China (No. 81320108008), the National Natural Science Foundation of China (No. 81270981) and the Science and Technology Program of Guangdong Province (No. 2013B051000029). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.