Celastrol inhibits migration, proliferation and transforming growth factor-β2-induced epithelial-mesenchymal transition in lens epithelial cells.
Int J Ophthalmol. 2019 ;12(10):1517-1523. Epub 2019 Oct 18. PMID: 31637185
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-model to find the function of celastrol further.
RESULTS: We found that celastrol inhibited the migration of LECs, as well as proliferation (<0.05). In addition, it induced the G2/M phase arrest by cell cycle-related proteins (<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.