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Sako, Keisuke,Fukuhara, Shigetomo,Minami, Takashi,Hamakubo, Takao,Song, Haihua,Kodama, Tatsuhiko,Fukamizu, Akiyoshi,Gutkind, J. Silvio,Koh, Gou Young,Mochizuki, Naoki American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.9
<P>Angiopoietin-1 (Ang1) regulates both vascular quiescence and angiogenesis through the receptor tyrosine kinase Tie2. We and another group have recently shown that Ang1 and Tie2 form distinct signaling complexes at cell-cell and cell-matrix contacts and further demonstrated that the former selectively induces expression of Krüppel-like factor 2 (KLF2), a transcription factor involved in vascular quiescence. Here, we investigated the mechanism of how Ang1/Tie2 signal induces KLF2 expression to clarify the role of KLF2 in Ang1/Tie2 signal-mediated vascular quiescence. Ang1 stimulated KLF2 promoter-driven reporter gene expression in endothelial cells, whereas it failed when a myocyte enhancer factor 2 (MEF2)-binding site of KLF2 promoter was mutated. Depletion of MEF2 by siRNAs abolished Ang1-induced KLF2 expression, indicating the requirement of MEF2 in KLF2 induction by Ang1. Constitutive active phosphoinositide 3-kinase (PI3K) and AKT increased the MEF2-dependent reporter gene expression by enhancing its transcriptional activity and stimulated the KLF2 promoter activity cooperatively with MEF2. Consistently, inhibition of either PI3K or AKT and depletion of AKT abrogated Ang1-induced KLF2 expression. In addition, we confirmed the dispensability of extracellular signal-regulated kinase 5 (ERK5) for Ang1-induced KLF2 expression. Furthermore, depletion of KLF2 resulted in the loss of the inhibitory effect of Ang1 on vascular endothelial growth factor (VEGF)-mediated expression of vascular cell adhesion molecule-1 in endothelial cells and VEGF-mediated monocyte adhesion to endothelial cells. Collectively, these findings indicate that Ang1/Tie2 signal stimulates transcriptional activity of MEF2 through a PI3K/AKT pathway to induce KLF2 expression, which may counteract VEGF-mediated inflammatory responses.</P>
Masao Fujiwara,Yuki Matsushita,Yoshikane Maeba,Ayano Suzuki,Hidekazu Fukamizu,Yoshiki Tokura 대한수부외과학회 2019 대한수부외과학회지 Vol.24 No.4
Purpose: First web space widening is crucial in the hand function. The skin on the dorsal side of the forearm can provide a thin and pliable skin suitable for first web space reconstruction. Although previous reports have described the use of the posterior interosseous artery (PIA) flap as a reverse-flow flap for treatment of first web space contracture, only a few have addressed its use as a free flap for this purpose. The caliber of the concomitant veins accompanying the PIA is usually small, which may give rise to a problem in the treatment.Methods: Seven patients with first web space contracture were treated with a free PIA flap and the details of the venous anastomosis method were elucidated.Results: Six of seven flaps survived. In a post-burn case, a flap was lost by late thrombosis. The PIA is anastomosed end-to-end to the dorsal branch of the radial artery. There are two choices for the recipient venous pedicle: concomitant veins of radial artery and a tributary of the cephalic vein. In our cases, there were four types of venous anastomosis. An average postoperative increase of the thumb radial abduction was 36° and that of the palmar abduction was 35°.Conclusion: Since the caliber of the concomitant veins accompanying the PIA is small, a careful scheme for venous anas-tomosis is essential in the treatment of first web space contracture using the free PIA flap.