Brahma-related gene 1 inhibits proliferation and migration of human aortic smooth muscle cells by directly up-regulating Ras-related associated with diabetes in the pathophysiologic processes of aortic dissection.
OBJECTIVE
To elucidate the mechanisms of Brahma-related gene 1 (Brg1) involvement in the pathophysiologic processes of aortic dissection.


METHODS
Seventeen dissecting, 4 dilated, and 10 healthy human aorta samples were collected. Expression of Brg1 in the medium of aorta was evaluated by quantitative real-time polymerase chain reaction, Western blot, and immunohistochemical staining, respectively. The regulation effect of Brg1 on proliferation and migration of human aortic smooth muscle cells (HASMCs) was analyzed in 3 ways: using cell counting, a migration chamber, and a wound scratch assay. A polymerase chain reaction array was used for screening potential target genes of Brg1. A chromatin immunoprecipitation assay was adopted for direct deoxyribonucleic acid-protein binding detection.


RESULTS
Expression levels of Brg1 were increased in aortic dissection and aortic dilation patients. In vitro results indicated that overexpression of Brg1 inhibited proliferation and migration of HASMCs. The candidate proliferation- and migration-related Brg1 target gene found was Ras-related associated with diabetes (RRAD), expression levels of which were enhanced in dissecting aortic specimens. The direct regulation effect of Brg1 on RRAD was verified by chromatin immunoprecipitation assay results. Furthermore, down-regulating RRAD significantly alleviated the suppression effects of Brg1 on proliferation and migration of HASMCs.


CONCLUSIONS
Our study illustrated that Brg1 inhibited the proliferation and migration capacity of HASMCs, via the mechanism of direct up-regulation of RRAD, thus playing an important role in the pathophysiologic processes of aortic dissection.
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Wei-Lin
WL
Liao
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Meng-Wei
MW
Tan
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Yang
Y
Yuan
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Guo-Kun
GK
Wang
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Chong
C
Wang
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China. Electronic address: dr_tanghao@vip.163.com.
Hao
H
Tang
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China. Electronic address: zhiyunx@hotmail.com.
Zhi-Yun
ZY
Xu
D000328:Adult; D000368:Aged; D000784:Aortic Dissection / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001014:Aortic Aneurysm / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism*
D009687:Nuclear Proteins; D012333:RNA, Messenger; C084355:RRAD protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases; D018631:ras Proteins
Brg1; RRAD; aortic dissection; human aortic smooth muscle cell; migration; proliferation