miR-22 contributes to endosulfan-induced endothelial dysfunction by targeting SRF in HUVECs.
microRNAs (miRNAs) function in the posttranscriptional gene regulation, providing new insights into the epigenetic mechanism of toxicity induced by environmental pollutants. miR-22 was discovered to regulate cell proliferation and apoptosis in response to environmental toxicants. We have reported that endosulfan can cause endothelial toxicity in human umbilical vein endothelial cells (HUVECs). In the present study, we investigated the involvement of miR-22 in endosulfan-induced endothelial dysfunction. The expression level of miR-22 was increased in a dose-dependent manner by endosulfan exposure. Overexpression of miR-22 induced apoptosis and inflammation in HUVECs. Anti-miR-22 transfection significantly attenuated the increase in the percentage of apoptotic cells, caspase-3 activity and Interleukin (IL)-6, 8 mRNA levels in endosulfan-exposed HUVECs. Luciferase reporter assay confirmed that SRF and STAG2 were novel direct targets of miR-22. Endosulfan decreased mRNA expression of both SRF and STAG2, but only suppressed protein expression of SRF. Knockdown of SRF via siRNAs resulted in apoptosis and inflammation whereas STAG2 siRNAs only caused abnormal mitosis in HUVECs. Taken together, these findings will shed light on the role and mechanism of miR-22 in endosulfan-induced endothelial dysfunction via SRF in HUVECs.
Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: jotan1995@163.com.
Dan
D
Xu
Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: 623302824@qq.com.
Yubing
Y
Guo
Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: liutong_555@163.com.
Tong
T
Liu
Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: lishuai19891115@163.com.
Shuai
S
Li
Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China. Electronic address: yqsun@dlmu.edu.cn.
Yeqing
Y
Sun
D000070416:Antagomirs / Q000494:pharmacology; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D004726:Endosulfan / Q000633:toxicity*; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D000097722:Cohesins
D000070416:Antagomirs; D034961:Antigens, Nuclear; D053148:Caspase 3; D018797:Cell Cycle Proteins; D004726:Endosulfan; D015850:Interleukin-6; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D026362:Serum Response Factor; C508600:IL6 protein, human; C548375:MIRN22 microRNA, human; C476858:SRF protein, human; C508565:STAG2 protein, human; D000097722:Cohesins; C505407:CASP3 protein, human
Apoptosis; Endosulfan; Endothelial dysfunction; Inflammation; miR-22