[Activation of sterol regulatory element binding protein and its involvement in endothelial cell migration].
OBJECTIVE
To study the activation of sterol regulatory element binding protein (SREBP) and its critical role in endothelial cell migration.


METHODS
Bovine aortic endothelial cells (ECs) were cultured. The expression of SREBP and Cdc42 were determined by Western blot and quantitative real-time PCR. Moreover, outward growth migration model and transwell chamber assay were used to detect ECs migration.


RESULTS
(1) SREBP was activated during ECs migration. Western blot analysis demonstrated increased active form SREBP in migrating as compared to non-migrating ECs population. SREBP activation decreased as ECs migration slowed;(2) Coincidental with SREBP activation, mRNA expression of its target genes such as low density lipoprotein receptor, HMG-CoA reductase, and fatty acid synthase also increased in migrating ECs population as detected by real-time PCR; (3) Migration induced SREBP activation in ECs was inhibited by SREBP-acting protein RNAi and pharmacologically by 25-hydroxycholesterol; (4) Inhibition of SREBP led to decreased ECs migration in various models; (5) Cells genetically deficient in SREBP-acting protein, S1P, or S2P, phenotypically exhibited impaired migration; (6) SREBP inhibition in ECs suppressed the activity of small GTPase Cdc42, a key molecule for ECs motility.


CONCLUSIONS
SREBP is activated during and plays a critical role in ECs migration. Targeting SREBP could become a novel approach in fighting diseases involving abnormal ECs migration.
Ma
Ya-bing
YB
Department of Geriatrics, Qilu Hospital of Shandong University, Jinan 250012, China.
Li
Bao-ying
BY
Gao
Hai-qing
HQ
Yao
Min
M
Koch
Walter J
WJ
Eckhart
Andrea D
AD
Zhou
Rui-hai
RH
D000818:Animals; D001011:Aorta / Q000166:cytology; D016466:CHO Cells; D002417:Cattle; D002465:Cell Movement; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D042783:Endothelial Cells; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D006888:Hydroxycholesterols / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism* / Q000502:physiology
D006888:Hydroxycholesterols; D012333:RNA, Messenger; D011973:Receptors, LDL; D051779:Sterol Regulatory Element Binding Proteins; C007997:25-hydroxycholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D064429:Fatty Acid Synthases