受賞区分：国際学会・会議・シンポジウム等の賞  受賞国：アメリカ合衆国

受賞区分：国際学会・会議・シンポジウム等の賞  受賞国：アメリカ合衆国

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Consecutive oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2 yields the hemiketal eicosanoids, HKE2 and HKD2. Hemiketals stimulate angiogenesis by inducing endothelial cell tubulogenesis in culture; however, how this process is regulated has not been determined. Here, we identify vascular endothelial growth factor receptor 2 (VEGFR2) as a mediator of HKE2-induced angiogenesis in vitro and in vivo. We found that HKE2 treatment of human umbilical vein endothelial cells dose-dependently increased the phosphorylation of VEGFR2 and the downstream kinases ERK and Akt that mediated endothelial cell tubulogenesis. In vivo, HKE2 induced the growth of blood vessels into polyacetal sponges implanted in mice. HKE2-mediated effects in vitro and in vivo were blocked by the VEGFR2 inhibitor vatalanib, indicating that the pro-angiogenic effect of HKE2 was mediated by VEGFR2. HKE2 covalently bound and inhibited PTP1B, a protein tyrosine phosphatase that dephosphorylates VEGFR2, thereby providing a possible molecular mechanism for how HKE2 induced pro-angiogenic signaling. In summary, our studies indicate that biosynthetic cross-over of the 5-lipoxygenase and cyclooxygenase-2 pathways gives rise to a potent lipid autacoid that regulates endothelial cell function in vitro and in vivo. These findings suggest that common drugs targeting the arachidonic acid pathway could prove useful in antiangiogenic therapy.

DOI： 10.1016/j.jbc.2023.103050

Web of Science

Scopus

PubMed

researchmap

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Chemical Society (ACS)  

DOI： 10.1021/jacsau.1c00177

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acsomega.4c03257

Web of Science

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bioscience, Biotechnology and Biochemistry  

Seabuckthorn pulp oil (SBO) is used in beauty products because of its rich lipophilic substances with high nutraceutical and cosmeceutical potential. However, the mechanism through which SBO enhances skin elasticity remains unclear. Therefore, in this study, we examined the anti-photoaging activity of SBO in normal human dermal fibroblasts (NHDF) under ultraviolet (UV) irradiation. Pretreatment with SBO significantly suppressed UV-B-induced cell toxicity and collagen degradation, suggesting that SBO contains anti-photoaging substances. Further, palmitoleic acid, the main component of SBO, maintained cell viability and collagen levels in UV-B-irradiated NHDF by suppressing the expression of matrix metalloproteinase 1 and acted on the inhibition of p38 and JNK phosphorylation and nuclear translocation of nuclear factor-kappa B. These findings suggest the utility of SBO as an anti-photoaging agent.

DOI： 10.1093/bbb/zbae071

Web of Science

Scopus

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Diabetic nephropathy (DN) is a major cause of chronic kidney disease. Microalbuminuria is currently the most common non-invasive biomarker for the early diagnosis of DN. However, renal structural damage may have advanced when albuminuria is detected. In this study, we sought biomarkers for early DN diagnosis through proteomic analysis of urinary extracellular vesicles (uEVs) from type 2 diabetic model rats and normal controls. Isocitrate dehydrogenase 1 (IDH1) was significantly increased in uEVs from diabetic model rats at the early stage despite minimal differences in albuminuria between the groups. Calorie restriction significantly suppressed the increase in IDH1 in uEVs and 24-hour urinary albumin excretion, suggesting that the increase in IDH1 in uEVs was associated with the progression of DN. Additionally, we investigated the origin of IDH1-containing uEVs based on their surface sugar chains. Lectin affinity enrichment and immunohistochemical staining showed that IDH1-containing uEVs were derived from proximal tubules. These findings suggest that the increase in IDH1 in uEVs reflects pathophysiological alterations in the proximal tubules and that IDH1 in uEVs may serve as a potential biomarker of DN in the proximal tubules.

DOI： 10.1096/fj.202400371R

Web of Science

Scopus

PubMed

researchmap

担当ページ：52-58   記述言語：日本語 著書種別：学術書

担当ページ：264-270   記述言語：日本語 著書種別：学術書

担当区分：筆頭著者   記述言語：英語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

DOI： 10.4327/jsnfs.77.125

記述言語：英語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

担当区分：筆頭著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

開催年月日： 2024年7月

記述言語：英語  

開催地：福岡   国名：日本国  

開催年月日： 2023年10月 - 2023年11月

記述言語：日本語   会議種別：ポスター発表  

開催年月日： 2023年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：広島   国名：日本国  

開催年月日： 2022年11月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：名古屋   国名：日本国  

開催年月日： 2020年

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Baltimore   国名：アメリカ合衆国