白内障 550 PO0011
Ultraviolet-B irradiation induced cellular apoptosis is mediated by TGF-β2 signaling pathway in cultured human lens epithelial cells
曹晓光、鲍永珍、黎晓新
北京大学人民医院眼科 100044
Background and purpose There is a strong association between ultraviolet-B (UVB) and human age-related cataract (HARC) formation. However, the underlying signaling mechanisms of UVB-induced damage in human lens epithelial cells (HLE) have not been fully examined. We therefore investigated signaling characteristics of transforming growth factor-β2(TGF-β2) and Smads (C. elegans, Sma; Drosophila mothers against dpp, Mad) signal pathway in a HLE line.
Methods ：Cells were starved for 24 hours prior to exposure to 480mW/cm2 UVB in the presence and absence of 0.01μg/ml AF-302-NA, a monoclonal anti-TGF-β2 neutralization antibody. Non-stimulated cells served as controls. Gene expression was assessed using reverse transcription-polymerase chain reaction (RT-PCR). Smad-4 localization was observed by immunocytochemistry. Cell apoptosis was examined by in situ immunocytochemistry using terminal deoxynucleotidyl transferase Dutp- mediated biotin nick end labeling (TUNEL) and by flow cytometer (FCM) using Annexin V-FITC apoptosis detection.
Results ：UVB-irradiation induced the accumulation of Smad-4 in cell nucleus, and upregulated the expression of TGF-β receptors (TβRs) Mrna in HLE, then upregulated the expression of apoptotic gene, bax, leading HLE to apoptosis. AF-302-NA decreased cellular apoptosis induced by UVB-irradiation in HLE and inhibit the translocation of Smad-4 to cell nucleus. Moreover, AF-302-NA not only upregulated the expression of TβRs Mrna but also downregulated the expression of bax Mrna in UVB-irradiated HLE.
Conclusion ：Our study demonstrated that TGF-β2 signal pathway partially transferred apoptotic signal and might be an initiator of cellular apoptosis after UVB irradiation on HLE. Interdiction TGF-β2 signal pathway could partially protect HLE from apoptosis induced by UVB-irradiation.
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