Effect of farrerol modulating JAK2/STAT3 signaling pathway on pyroptosis of lens epithelial cells induced by hydrogen peroxide
10.16098/j.issn.0529-1356.2025.02.008
- VernacularTitle:杜鹃素调节JAK2/STAT3信号通路对过氧化氢诱导晶状体上皮细胞焦亡的影响
- Author:
Jia JIA
1
;
Lin-Chang ZHANG
;
Hai-Xia ZHANG
Author Information
1. 天津市第五中心医院(北京大学滨海医院)眼科,天津 300450
- Keywords:
Cataract;
Lens epithelial cell;
Farrerol;
Janus kinase 2/single transducers and activator of transcription 3 signal pathway;
Enzyme linked immunosorbent assay;
Rat
- From:
Acta Anatomica Sinica
2025;56(2):180-187
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of farrerol on pyroptosis induced by hydrogen peroxide(H2O2)in lens epithelial cells through regulating JAK2/STAT3 signaling pathway.Methods Thirty-six neonatal SD rats were randomly divided into normal group,cataract group(20 μmol/kg sodium selenite),farrerol low dose,medium dose and high dose groups(10,20,40 mg/kg farrerol)and positive control group(benzyda lysine eye drops).Lens turbidity was observed by slit-lamp and scored,and pathological changes of lens were observed by HE staining.Human lens epithelial cells were cultured and divided into control group,model group,low concentration farrerol group(20 mg/L),high concentration farrerol group(40 mg/L),high concentration farrerol+R08191 group(40 mg/L+10 μmol/L),except the control group,other groups were induced by H2O2.The cell activity was detected by CCK-8 method;the concentrations of interleukin(IL-1 β)and IL-18 in cell culture medium were measured by ELISA;inverted phase contrast microscope was used to observe the cell scorch in each group;The expression of N-terminal fragment of GSDMD(GSDMD-N)protein was detected by immunofluorescent staining;the content of reactive ozygen species(ROS)was measured by flow cytometry;the expressions of latent heat protein(NLRP3),apoptosis-associate speck-like protein containing a CARD(ASC),Caspase-1,GSDMD-N,JAK2/STAT3 pathway proteins were detected by Western blotting.Results In cataract rats,the lens epithelial cells were disorderly and loosely arranged,the lens fibrosis/liquefaction,and the lens turbidity score increased(P＜0.05).Compared with the cataract group,the lens damage and the lens turbidity score decreased in the low,medium and farrerol high dose group and the positive control group(P＜0.05),and the effect of the farrerol high dose group was the best,which was basically consistent with the positive control group.The cells in the control group were closely connected and arranged in order,without scorched cells;in the model group,the cells were swollen and had typical charring characteristics of bubble like protrusion;Compared with the model group,the cell bubble protrusion in the low concentration farrerol group and the high concentration farrerol group was alleviated;Compared with the high concentration farrerol group,the cell bubble protrusion in the high concentration farrerol+R08191 group was aggravated.Compared with the control group,the cell survival rate in model group was decreased,the levels of IL-18 and IL-1 β in supernatant,the number of GSDMD-N positive cells,the level of ROS,the expression of NLPR3,ASC,Caspase-1,GSDMD-N protein,p-JAK2/JAK2,p-STAT3/STAT3 were increased(P＜0.05);Compared with the model group,the cell survival rate in the low concentration farrerol group and the high concentration farrerol group was increased,the levels of IL-18 and IL-1β in supernatant,the number of GSDMD-N positive cells,the level of ROS,the expression of NLPR3,ASC,Caspase-1,GSDMD-N protein,p-JAK2/JAK2,p-STAT3/STAT3 were decreased(P＜0.05);compared with the high concentration farrerol group,the cell survival rate in the high concentration farrerol+R08191 group was decreased,the levels of IL-18 and IL-1 β in supernatant,the number of GSDMD-N positive cells,the level of ROS,the expression of NLPR3,ASC,Caspase-1,GSDMD-N protein,p-JAK2/JAK2,p-STAT3/STAT3 signaling were increased(P＜0.05).Conclusion Farrerol may inhibit H2O2-induced pyroptosis of lens epithelial cells by inhibiting JAK2/STAT3 signaling pathway.
