Induction of microRNA-138 by pro-inflammatory Cytokines causes Endothelial Cell Dysfunction.

FEBS letters (Impact Factor: 3.17). 01/2014; 588(6). DOI: 10.1016/j.febslet.2014.01.033
Source: PubMed


Exposure to pro-inflammatory cytokines, such as angiotensin II, endothelin-1 or TNF leads to endothelial dysfunction, characterized by the reduced production of nitric oxide via endothelial nitric oxide synthase (eNOS). We recently identified the Ca(2+) binding protein S100A1 as an essential factor required for eNOS activity. Here we report that pro-inflammatory cytokines down-regulate expression of S100A1 in primary human microvascular endothelial cells (HMVECs) via induction of microRNA-138 (miR-138), in a manner that depends on the stabilization of HIF1-α. We show that loss of S100A1 in ECs reduces stimulus-induced NO production, which can be prevented by inhibition of miR-138. Our study suggests that targeting miR-138 might be beneficial for the treatment of cardiovascular disease.

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    • "In colorectal and ovarian cancers, miR-138 suppressed cancer cell migration and metastasis through interfered with TWIST2, SOX4 and HIF1-a [39], [41]. Most recent studies reported that downregulated miR-138 sustained inflammatory factor NF-kB activation and promoted esophageal cancer progression [42], and that miR-138 response to pro-inflammatory cytokines depends on the stabilization of HIF1-α in primary human microvascular endothelial cells [43]. miR-145 is also a tumor suppressor gene. "
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