Down-regulation of SENCR promotes smooth muscle cells proliferation and migration in db/db mice through up-regulation of FoxO1 and TRPC6.
BACKGROUND
The inappropriate proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in the atherosclerotic process. SENCR was reported to be associated with cell migration in human smooth muscle cells. However, the regulation role of SENCR in SMCs is still not fully understood.


METHODS
qRT-PCR and Western blotting were performed to detect the mRNA and protein levels of SENCR, FOXO1 and TRPC6 in SMCs of db/db mice and SMCs exposed to high glucose. The regulation of SENCR on the expression of FoxO1 and TRPC6 were examined with luciferase report assays. Furthermore, we investigated the effect of SENCR on VSMCs proliferation and migration using MTT assay and cell migration assay, respectively.


RESULTS
Here, we found that SENCR was down-regulated in db/db mice and in SMCs exposed to high glucose. According to the result of luciferase assays, it was shown that SMCs knockdown enhanced the expression of FoxO1 and FoxO1 overexpression increased the expression of TRPC6. In addition, qRT-PCR revealed that SENCR overexpression reversed the effect of high glucose on mouse VSMCs proliferation and migration.


CONCLUSIONS
In this study, our data indicated that down-regulation of SENCR promoted smooth muscle cells proliferation and migration in db/db mice through up-regulation of FoxO1 and TRPC6.
Department of Anesthesiology, Changzhou No. 2 People's Hospital, No. 29, Xinglong Lane, Tianning District, 213003 Changzhou, Jiangsu Province, P.R. China.
Zhi-Qing
ZQ
Zou
Department of Anesthesiology, Changzhou No. 2 People's Hospital, No. 29, Xinglong Lane, Tianning District, 213003 Changzhou, Jiangsu Province, P.R. China.
Juan
J
Xu
Department of Anesthesiology, Changzhou No. 2 People's Hospital, No. 29, Xinglong Lane, Tianning District, 213003 Changzhou, Jiangsu Province, P.R. China.
Li
L
Li
Department of Anesthesiology, Changzhou No. 2 People's Hospital, No. 29, Xinglong Lane, Tianning District, 213003 Changzhou, Jiangsu Province, P.R. China. Electronic address: yeshanhan123@163.com.
Ye-Shan
YS
Han
D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology*; D015536:Down-Regulation; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000008:administration & dosage; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000235:genetics; D000074287:TRPC6 Cation Channel; D015854:Up-Regulation
D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; D005947:Glucose
FoxO1; Migration; Proliferation; SENCR; Smooth muscle cells; TRPC6