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Updated: Jun 27, 2026

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Possible involvement of corticotropin-releasing factor receptor signaling on vascular inflammation
Yuri Inada1, Keiichi Ikeda, Katsuyoshi Tojo
1Division of Diabetes and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Abstract:
Based on the reported anti-inflammatory and anti-stress responses by corticotropin-releasing factor (CRF) receptor signaling, endogenous CRF receptor agonists, CRF, urocortin (UCN) I and its related peptides, may play protective roles against cardiovascular stresses via the CRF receptor signaling. Therefore, the present study was designed to evaluate the involvement of CRF receptor signaling against vascular inflammatory stress using human aortic endothelial cells (HAECs). In addition, due to the possible involvement of CRF receptor signaling in the effects of statin on endothelial cells, the effects of pitavastatin on the expression of UCN-related peptides in HAECs were also evaluated. HAECs expressed all UCNs, CRF type 1 receptor (CRF-R1), and CRF type 2 (CRF-R2)alpha and CRF-R2beta mRNAs. Real time PCR analysis revealed that UCN I mRNA was down-regulated, whereas UCN II mRNA was up-regulated by tumor necrosis factor (TNF)-alpha. Selective blockade of CRF-R1 resulted in significant increase in TNF-alpha-induced expression of vascular adhesion molecule-1 at mRNA level and E-selectin at mRNA and protein levels. Pitavastatin up-regulated UCN I mRNA without TNF-alpha, but co-incubation with pitavastatin and TNF-alpha resulted in decrease in UCN I mRNA. On the contrary, UCN II, CRF-R1, and CRF-R2 mRNAs were markedly increased by co-incubation of pitavastatin and TNF-alpha. These facts indicate that CRF-R1 signaling may have protective role against TNF-alpha-induced vascular inflammation. In addition, because of up-regulation of CRF-R1 mRNA by pitavastatin with or without TNF-alpha, CRF-R1 may be involved in the vasoprotective effects of pitavastatin.
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