Activation of sterol regulatory element binding protein and its involvement in endothelial cell migration / 中华病理学杂志
Chinese Journal of Pathology
;
(12): 50-54, 2009.
Article
in Chinese
| WPRIM
| ID: wpr-319792
ABSTRACT
<p><b>OBJECTIVE</b>To study the activation of sterol regulatory element binding protein (SREBP) and its critical role in endothelial cell migration.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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.</p><p><b>CONCLUSIONS</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Aorta
/
Pharmacology
/
Physiology
/
RNA, Messenger
/
Receptors, LDL
/
Cell Movement
/
Cells, Cultured
/
Cricetulus
/
CHO Cells
/
Cell Biology
Limits:
Animals
Language:
Chinese
Journal:
Chinese Journal of Pathology
Year:
2009
Type:
Article
Similar
MEDLINE
...
LILACS
LIS