Celastrol inhibits migration, proliferation and transforming growth factor-β2-induced epithelial-mesenchymal transition in lens epithelial cells

• Main Authors: Li-Ping Wang, Bao-Xin Chen, Yan Sun, Jie-Ping Chen, Shan Huang, Yi-Zhi Liu
• Format: Article
• Language: English
• Published: Press of International Journal of Ophthalmology (IJO PRESS) 2019-10-01
• Series: International Journal of Ophthalmology
• Subjects: lens; cataract; fibrosis; transforming growth factor-β2; celastrol
• Online Access: http://www.ijo.cn/en_publish/2019/10/20191001.pdf

AIM: To investigate the mechanism of celastrol in inhibiting lens epithelial cells (LECs) fibrosis, which is the pathological basis of cataract. METHODS: Human LEC line SRA01/04 was treated with celastrol and transforming growth factor-β2 (TGF-β2). Wound-healing assay, proliferation assay, flow cytometry, real-time polymerase chain reaction (PCR), Western blot and immunocytochemical staining were used to detect the pathological changes of celastrol on LECs. Then, we cultured Sprague-Dawley rat lens in medium as a semi-in vivo model to find the function of celastrol further. RESULTS: We found that celastrol inhibited the migration of LECs, as well as proliferation (P<0.05). In addition, it induced the G2/M phase arrest by cell cycle-related proteins (P<0.01). Moreover, celastrol inhibited epithelial-mesenchymal transition (EMT) by the blockade of TGF-β/Smad and Jagged/Notch signaling pathways. CONCLUSION: Our study demonstrates that celastrol could inhibit TGF-β2-induced lens fibrosis and raises the possibility that celastrol could be a potential novel drug in prevention and treatment of fibrotic cataract.