Inhibition of cell proliferation, migration and apoptosis in blue-light illuminated human retinal pigment epithelium cells by down-regulation of HtrA1

被引:0
作者
Yu, Tian [1 ]
Chen, Chang-Zheng [1 ]
Xing, Yi-Qiao [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Ctr Eye, 238 Jiefang Rd, Wuhan 430060, Hubei Province, Peoples R China
基金
中国国家自然科学基金;
关键词
HtrA; 1; retinal pigment epithelium; small interfering RNA; AGE-RELATED MACULOPATHY; SERINE-PROTEASE HTRA1; MACULAR DEGENERATION; PROTECTION; IMPACT; CANCER; DAMAGE; EYE;
D O I
10.18240/1jo.2017.04.04
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
AIM: To investigate the effect of HtrA1 on the proliferation, migration and apoptosis of human retinal pigment epithelium (RPE) cells in the light injured model, as well as the expression of the apoptosis related molecules. METHODS: The human RPE cell line ARPE-19 was exposed to blue light to establish the light injured model. The cells were transfected with HtrA1 siRNA to knockdown HtrA1 expression. Subsequent expression of HtrA1 was determined by real-time polymerase chain reaction (RTPCR) and Western blot, respectively. Changes in cell proliferation, migration and apoptosis were assessed by cell counting kit-8 (CCK-8), Transwell assay and flow cytometry respectively, as well as changes in the mRNA and protein levels of Bax, Caspase-3 and Bcl-2 expression. RESULTS: HtrA1 was highly expressed in ARPE-19 cells after blue light irradiation. Knockdown of HtrA1 expression inhibited the proliferation, migration and apoptosis of the blue-light-irradiated ARPE-19 cells (P<0.05). Bax and Caspase-3 expression were significantly reduced both at mRNA and protein levels (P<0.05) after siRNA treatment. Bcl-2 expression significantly increased in blue-light irradiated ARPE-19 cells after siRNA interference (P<0.05). CONCLUSION: Silence of HtrA1 may inhibit the proliferation, migration and apoptosis of ARPE-19 cells in light injured model. Moreover, HtrA1 suppression in blue-light irradiated ARPE-19 cells may ameliorate cell apoptosis through down-regulation of Bax and Caspase-3, and up regulation of Bcl-2 expression.
引用
收藏
页码:524 / 529
页数:6
相关论文
共 34 条
[1]   Age-related maculopathy and the impact of blue light hazard [J].
Algvere, PV ;
Marshall, J ;
Seregard, S .
ACTA OPHTHALMOLOGICA SCANDINAVICA, 2006, 84 (01) :4-15
[2]   The HtrA1 serine protease is down-regulated during human melanoma progression and represses growth of metastatic melanoma cells [J].
Baldi, A ;
De Luca, A ;
Morini, M ;
Battista, T ;
Felsani, A ;
Baldi, F ;
Catricalà, C ;
Amantea, A ;
Noonan, DM ;
Albini, A ;
Natali, PG ;
Lombardi, D ;
Paggi, MG .
ONCOGENE, 2002, 21 (43) :6684-6688
[3]   Age-related macular degeneration: genome-wide association studies to translation [J].
Black, James R. M. ;
Clark, Simon J. .
GENETICS IN MEDICINE, 2016, 18 (04) :283-289
[4]  
[蔡善君 CAI Shanjun], 2005, [中华眼底病杂志, Chinese Journal of Ocular Fundus Diseases], V21, P384
[5]   A candidate tumor suppressor HtrA1 is downregulated in ovarian cancer [J].
Chien, J ;
Staub, J ;
Hu, SI ;
Erickson-Johnson, MR ;
Couch, FJ ;
Smith, DI ;
Crowl, RM ;
Kaufmann, SH ;
Shridhar, V .
ONCOGENE, 2004, 23 (08) :1636-1644
[6]   HtrA Serine Proteases as Potential Therapeutic Targets in Cancer [J].
Chien, Jeremy ;
Campioni, Mara ;
Shridhar, Viji ;
Baldi, Alfonso .
CURRENT CANCER DRUG TARGETS, 2009, 9 (04) :451-468
[7]   Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity [J].
Chien, Jeremy ;
Aletti, Giovanni ;
Baldi, Alfonso ;
Catalano, Vincenzo ;
Muretto, Pietro ;
Keeney, Gary L. ;
Kalli, Kimberly R. ;
Staub, Julie ;
Ehrmann, Michael ;
Cliby, William A. ;
Lee, Yean Kit ;
Bible, Keith C. ;
Hartmann, Lynn C. ;
Kaufmann, Scott H. ;
Shridhar, Viji .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (07) :1994-2004
[8]   The HtrA family of proteases: Implications for protein composition and cell fate [J].
Clausen, T ;
Southan, C ;
Ehrmann, M .
MOLECULAR CELL, 2002, 10 (03) :443-455
[9]   Distribution of the serine protease HtrA1 in normal human tissues [J].
De Luca, A ;
De Falco, M ;
Severino, A ;
Campioni, M ;
Santini, D ;
Baldi, F ;
Paggi, MG ;
Baldi, A .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2003, 51 (10) :1279-1284
[10]   Blue light induces mitochondrial DNA damage and free radical production in epithelial cells [J].
Godley, BF ;
Shamsi, FA ;
Liang, FQ ;
Jarrett, SG ;
Davies, S ;
Boulton, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (22) :21061-21066