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4. Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy

Author

Morinaga, Jun, Kashiwabara, Kosuke, Torigoe, Daisuke, Okadome, Yusuke, Aizawa, Kenichi, Uemura, Kohei, Kurashima, Ai, Matsunaga, Eiji, Fukami, Hirotaka, Horiguchi, Haruki, Sato, Michio, Sugizaki, Taichi, Miyata, Keishi, Kadomatsu, Tsuyoshi, Mukoyama, Masashi, Miyauchi, Katsumi, Hokimoto, Seiji, Fukumoto, Yoshihiro, Hiro, Takafumi, Hibi, Kiyoshi, Nakagawa, Yoshihisa, Sakuma, Ichiro, Ozaki, Yukio, Iwata, Hiroshi, Iimuro, Satoshi, Daida, Hiroyuki, Shimokawa, Hiroaki, Kimura, Takeshi, Matsuzaki, Masunori, Saito, Yasushi, Matsuyama, Yutaka, Nagai, Ryozo, and Oike, Yuichi

Published
2023
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8. The lncRNA Caren antagonizes heart failure by inactivating DNA damage response and activating mitochondrial biogenesis

Author

Sato, Michio, Kadomatsu, Tsuyoshi, Miyata, Keishi, Warren, Junco S., Tian, Zhe, Zhu, Shunshun, Horiguchi, Haruki, Makaju, Aman, Bakhtina, Anna, Morinaga, Jun, Sugizaki, Taichi, Hirashima, Kaname, Yoshinobu, Kumiko, Imasaka, Mai, Araki, Masatake, Komohara, Yoshihiro, Wakayama, Tomohiko, Nakagawa, Shinichi, Franklin, Sarah, Node, Koichi, Araki, Kimi, and Oike, Yuichi

Published
2021
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9. ANGPTL2‐mediated epigenetic repression of MHC‐I in tumor cells accelerates tumor immune evasion

Author

Kadomatsu, Tsuyoshi, primary, Hara, Chiaki, additional, Kurahashi, Ryoma, additional, Horiguchi, Haruki, additional, Morinaga, Jun, additional, Miyata, Keishi, additional, Kurano, Sohtaro, additional, Kanemaru, Hisashi, additional, Fukushima, Satoshi, additional, Araki, Kimi, additional, Baba, Masaya, additional, Linehan, W. Marston, additional, Kamba, Tomomi, additional, and Oike, Yuichi, additional

Published
2023
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15. Aortic carboxypeptidase-like protein, a WNT ligand, exacerbates nonalcoholic steatohepatitis

Author

Teratani, Toshiaki, Tomita, Kengo, Suzuki, Takahiro, Furuhashi, Hirotaka, Irie, Rie, Nishikawa, Makoto, Yamamoto, Junji, Hibi, Toshifumi, Miura, Soichiro, Minamino, Tohru, Oike, Yuichi, Hokari, Ryota, and Kanai, Takanori

Subjects
Liver diseases -- Genetic aspects -- Development and progression -- Care and treatment, Cellular proteins -- Health aspects, Cellular signal transduction -- Genetic aspects -- Health aspects, Health care industry
Abstract

Incidence of nonalcoholic steatohepatitis (NASH), which is considered a hepatic manifestation of metabolic syndrome, has been increasing worldwide with the rise in obesity; however, its pathological mechanism is poorly understood. Here, we demonstrate that the hepatic expression of aortic carboxypeptidase-like protein (ACLP), a glycosylated, secreted protein, increases in NASH in humans and mice. Furthermore, we elucidate that ACLP is a ligand, unrelated to WNT proteins, that activates the canonical WNT pathway and exacerbates NASH pathology. In the liver, ACLP is specifically expressed in hepatic stellate cells (HSCs). As fatty liver disease progresses, ACLP expression is enhanced via activation of STAT3 signaling by obesity-related factors in serum. ACLP specifically binds to frizzled-8 and low- density lipoprotein-related receptor 6 to form a ternary complex that activates canonical WNT signaling. Consequently, ACLP activates HSCs by inhibiting PPARy signals. HSC-specific ACLP deficiency inhibits fibrosis progression in NASH by inhibiting canonical WNT signaling in HSCs. The present study elucidates the role of canonical WNT pathway activation by ACLP in NASH pathology, indicating that NASH can be treated by targeting ACLP-induced canonical WNT pathway activation in HSCs., Introduction Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Currently, NAFLD is the most prevalent liver disease in the world, with an estimated 1 billion [...]

Published
2018
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19. Serum Angiopoietin-Like Protein 2 and NT-Pro BNP Levels and Their Associated Factors in Patients with Chronic Heart Failure Participating in a Phase III Cardiac Rehabilitation Program

Author

Tanaka, Chiharu, Kurose, Satoshi, Morinaga, Jun, Takao, Nana, Miyauchi, Takumi, Tsutsumi, Hiromi, Shiojima, Ichiro, Oike, Yuichi, and Kimura, Yutaka

Subjects
Heart Failure, Inflammation, Male, Cardiac Rehabilitation, Exercise Tolerance, Anaerobic Threshold, Hand Strength, Stroke Volume, Blood Proteins, Middle Aged, Peptide Fragments, Ventricular Function, Left, Angiopoietin-like Proteins, C-Reactive Protein, Cross-Sectional Studies, Echocardiography, Case-Control Studies, Chronic Disease, Multivariate Analysis, Natriuretic Peptide, Brain, Body Composition, Humans, Female, Biomarkers, Aged
Abstract

令和3年度, Angiopoietin-like protein 2 (ANGPTL2) promotes chronic inflammation and plays a key role in the pathogenesis of heart failure. Cardiac rehabilitation (CR) is an integral component of heart failure management and has been shown to have anti-inflammatory effects. However, ANGPTL2 concentration in chronic heart failure patients undergoing CR has not been evaluated. This study aimed to investigate serum ANGPTL2 levels and their associated factors and compare the results with those of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure undergoing phase III CR.A total of 56 patients were enrolled. Clinical characteristics including body composition, grip strength, exercise tolerance, duration of CR, blood counts and biochemistry, and echocardiographic parameters were evaluated for their association with serum ANGPTL2 and NT-proBNP levels.The median (first and third quartiles) value of ANGPTL2 was 4.05 (2.70-5.57) ng/mL. Clinical parameters that correlated with serum ANGPTL2 levels were body weight, body mass index, body fat mass, body fat percentage, anaerobic threshold (AT), C-reactive protein, and total protein (TP), which were mostly distinct from those that correlated with serum NT-proBNP levels. A multivariate analysis revealed that AT and TP were independent factors related to ANGPTL2 levels, whereas age, left ventricular ejection fraction, and left atrial dimension were independently related to NT-proBNP levels.These observations suggest that CR increases the exercise tolerance and exhibits anti-inflammatory effects simultaneously, and this situation is reflected by decreased serum ANGPLT2 and TP levels. ANGPTL2 may be a useful marker of inflammation and impaired exercise tolerance in patients with chronic heart failure.

Published
2021

20. The Adipocyte-Inducible Secreted Phospholipases PLA2G5 and PLA2G2E Play Distinct Roles in Obesity

Author

Sato, Hiroyasu, Taketomi, Yoshitaka, Ushida, Ayako, Isogai, Yuki, Kojima, Takumi, Hirabayashi, Tetsuya, Miki, Yoshimi, Yamamoto, Kei, Nishito, Yasumasa, Kobayashi, Tetsuyuki, Ikeda, Kazutaka, Taguchi, Ryo, Hara, Shuntaro, Ida, Satoshi, Miyamoto, Yuji, Watanabe, Masayuki, Baba, Hideo, Miyata, Keishi, Oike, Yuichi, Gelb, Michael H., and Murakami, Makoto

Published
2014
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21. Targeting chemoresistance in Xp11.2 translocation renal cell carcinoma using a novel polyamide–chlorambucil conjugate

Author

Funasaki, Shintaro, primary, Mehanna, Sally, additional, Ma, Wenjuan, additional, Nishizawa, Hidekazu, additional, Kamikubo, Yasuhiko, additional, Sugiyama, Hiroshi, additional, Ikeda, Shuji, additional, Motoshima, Takanobu, additional, Hasumi, Hisashi, additional, Linehan, W. Marston, additional, Schmidt, Laura S., additional, Ricketts, Chris, additional, Suda, Toshio, additional, Oike, Yuichi, additional, Kamba, Tomomi, additional, and Baba, Masaya, additional

Published
2022
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22. Plasma Angiopoietin-Like Protein 2 Levels and Mortality Risk Among Younger-Old Japanese People : A Population-Based Case-Cohort Study

Author

Zhao, Wenjing, Morinaga, Jun, Ukawa, Shigekazu, Endo, Motoyoshi, Yamada, Hiroya, Kawamura, Takashi, Wakai, Kenji, Tsushita, Kazuyo, Ando, Masahiko, Suzuki, Koji, Oike, Yuichi, 1000090236737, Tamakoshi, Akiko, Zhao, Wenjing, Morinaga, Jun, Ukawa, Shigekazu, Endo, Motoyoshi, Yamada, Hiroya, Kawamura, Takashi, Wakai, Kenji, Tsushita, Kazuyo, Ando, Masahiko, Suzuki, Koji, Oike, Yuichi, 1000090236737, and Tamakoshi, Akiko

Abstract

Aging is an important medical and social problem. Excessive angiopoietin-like protein (ANGPTL)-2 signaling causes chronic tissue inflammation, promoting development and progression of aging-related diseases. Moreover, circulating ANGPTL2 levels reportedly predict the risk of some aging-related diseases and subsequent death. However, there are, as yet, no reports of whether circulating ANGPTL2 levels predict vital prognosis in younger-old, community-dwelling populations. This study investigated associations between plasma ANGPTL2 levels and all-cause and specific-cause mortality in this population. The case-cohort study was abstracted from an ongoing, age-specific prospective cohort study: the New Integrated Suburban Seniority Investigation Project. This project enrolled 3 073 participants aged 64 years at the beginning of the investigation from 1996 through 2005. A subcohort of 714 randomly sampled participants plus 387 cases representing deceased participants followed through 2015 underwent survival analysis. Plasma ANGPTL2 concentrations were positively associated with >80% and 100% higher risk of all-cause mortality and cancer mortality, respectively, after adjustment for gender, smoking, alcohol consumption, walking time, sleep duration, caloric intake, medical status, disease history, BMI, and triglyceride, creatinine, uric acid, and high sensitivity C-reactive protein levels. A more robust association between ANGPTL2 levels and all-cause and cancer mortality was seen in participants with either frailties or with lifestyles of heavier drinking or current smoking. Elevated plasma ANGPTL2 levels are associated with high all-cause and cancer mortality in a community-dwelling sample of younger-old adults. These findings expand our knowledge of human aging and associated diseases.

Published
2022

25. Impaired Insulin Signaling in Endothelial Cells Reduces Insulin-Induced Glucose Uptake by Skeletal Muscle

Author

Kubota, Tetsuya, Kubota, Naoto, Kumagai, Hiroki, Yamaguchi, Shinichi, Kozono, Hideki, Takahashi, Takehiro, Inoue, Mariko, Itoh, Shinsuke, Takamoto, Iseki, Sasako, Takayoshi, Kumagai, Katsuyoshi, Kawai, Tomoko, Hashimoto, Shinji, Kobayashi, Tsuneo, Sato, Maki, Tokuyama, Kumpei, Nishimura, Satoshi, Tsunoda, Masaki, Ide, Tomohiro, Murakami, Koji, Yamazaki, Tomomi, Ezaki, Osamu, Kawamura, Koichi, Masuda, Hirotake, Moroi, Masao, Sugi, Kaoru, Oike, Yuichi, Shimokawa, Hiroaki, Yanagihara, Nobuyuki, Tsutsui, Masato, Terauchi, Yasuo, Tobe, Kazuyuki, Nagai, Ryozo, Kamata, Katsuo, Inoue, Kenji, Kodama, Tatsuhiko, Ueki, Kohjiro, and Kadowaki, Takashi

Published
2011
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26. Hyperglycemia and Thrombocytopenia ― Combinatorially Increase the Risk of Mortality in Patients With Acute Myocardial Infarction Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation ―

Author

Okadome, Yusuke, primary, Morinaga, Jun, additional, Fukami, Hirotaka, additional, Hori, Kota, additional, Ito, Teruhiko, additional, Sato, Michio, additional, Miyata, Keishi, additional, Kuwabara, Takashige, additional, Mukoyama, Masashi, additional, Suzuki, Ryusuke, additional, Tsunoda, Ryusuke, additional, and Oike, Yuichi, additional

Published
2021
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28. Angiopoietin-like Protein 2 Promotes Chronic Adipose Tissue Inflammation and Obesity-Related Systemic Insulin Resistance

Author

Tabata, Mitsuhisa, Kadomatsu, Tsuyoshi, Fukuhara, Shigetomo, Miyata, Keishi, Ito, Yasuhiro, Endo, Motoyoshi, Urano, Takashi, Zhu, Hui Juan, Tsukano, Hiroto, Tazume, Hirokazu, Kaikita, Koichi, Miyashita, Kazuya, Iwawaki, Takao, Shimabukuro, Michio, Sakaguchi, Kazuhiko, Ito, Takaaki, Nakagata, Naomi, Yamada, Tetsuya, Katagiri, Hideki, Kasuga, Masato, Ando, Yukio, Ogawa, Hisao, Mochizuki, Naoki, Itoh, Hiroshi, Suda, Toshio, and Oike, Yuichi

Published
2009
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31. Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver

Author

Onoyama, Ichiro, Suzuki, Atsushi, Matsumoto, Akinobu, Tomita, Kengo, Katagiri, Hideki, Oike, Yuichi, Nakayama, Keiko, and Nakayama, Keiichi I.

Subjects
Cell proliferation -- Research, Genes -- Physiological aspects -- Research, Liver -- Genetic aspects -- Physiological aspects -- Research, Lipid metabolism -- Genetic aspects -- Research, Health care industry
Abstract

E3 ubiquitin ligase complexes of the SCF type consist of ring-box 1 (Rbx1), cullin 1 (Cul1), S-phase kinase-associated protein 1 (Skp1), and a member of the F-box family of proteins. The identity of the F-box protein determines the substrate specificity of the complex. The F-box family member F-box- and WD repeat domain-containing 7 (Fbxw7; also known as Fbw7, SEL-10, hCdc4, and hAgo) targets for degradation proteins with wide-ranging functions, and uncovering its in vivo role has been difficult, because [Fbxw7.sup.-/-] embryos die in utero. Using two different Cre-loxP systems (Mx1-Cre and Alb-Cre), we generated mice with liver-specific null mutations of Fbxw7. Hepatic ablation of Fbxw7 resulted in hepatomegaly and steatohepatitis, with massive deposition of triglyceride, a phenotype similar to that observed in humans with nonalcoholic steatohepatitis. Both cell proliferation and the abundance of Fbxw7 substrates were increased in the Fbxw7-deficient liver. Long-term Fbxw7 deficiency resulted in marked proliferation of the biliary system and the development of hamartomas. Fbxw7 deficiency also skewed the differentiation of liver stem cells toward the cholangiocyte lineage rather than the hepatocyte lineage in vitro. This bias was corrected by additional loss of the Notch cofactor RBP-J, suggesting that Notch accumulation triggered the abnormal proliferation of the biliary system. Together, our results suggest that Fbxw7 plays key roles, regulating lipogenesis and cell proliferation and differentiation in the liver., Introduction The abundance of cellular proteins is regulated in a coordinated manner at the levels of their synthesis and degradation. In particular, intracellular proteolysis is thought to be subject to [...]

Published
2011
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32. Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1

Author

Iwabu, Masato, Yamauchi, Toshimasa, Okada-Iwabu, Miki, Sato, Koji, Nakagawa, Tatsuro, Funata, Masaaki, Yamaguchi, Mamiko, Namiki, Shigeyuki, Nakayama, Ryo, Tabata, Mitsuhisa, Ogata, Hitomi, Kubota, Naoto, Takamoto, Iseki, Hayashi, Yukiko K., Yamauchi, Naoko, Waki, Hironori, Fukayama, Masashi, Nishino, Ichizo, Tokuyama, Kumpei, Ueki, Kohjiro, Oike, Yuichi, Ishii, Satoshi, Hirose, Kenzo, Shimizu, Takao, Touhara, Kazushige, and Kadowaki, Takashi

Published
2010
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33. A crucial role for adipose tissue p53 in the regulation of insulin resistance

Author

Minamino, Tohru, Orimo, Masayuki, Shimizu, Ippei, Kunieda, Takeshige, Yokoyama, Masataka, Ito, Takashi, Nojima, Aika, Nabetani, Akira, Oike, Yuichi, Matsubara, Hisahiro, Ishikawa, Fuyuki, and Komuro, Issei

Subjects
Telomerase -- Research, Telomerase -- Physiological aspects, Cellular control mechanisms -- Research, Cellular control mechanisms -- Physiological aspects, Insulin resistance -- Physiological aspects, Insulin resistance -- Research, Adipose tissues -- Research, Adipose tissues -- Physiological aspects
Abstract

Various stimuli, such as telomere dysfunction and oxidative stress, can induce irreversible cell growth arrest, which is termed 'cellular senescence' (1,2). This response is controlled by tumor suppressor proteins such as p53 and pRb. There is also evidence that senescent cells promote changes related to aging or age-related diseases (3-6). Here we show that p53 expression in adipose tissue is crucially involved in the development of insulin resistance, which underlies age-related cardiovascular and metabolic disorders. We found that excessive calorie intake led to the accumulation of oxidative stress in the adipose tissue of mice with type 2 diabetes-like disease and promoted senescence-like changes, such as increased activity of senescence-associated [beta]-galactosidase, increased expression of p53 and increased production of proinflammatory cytokines. Inhibition of p53 activity in adipose tissue markedly ameliorated these senescence-like changes, decreased the expression of proinflammatory cytokines and improved insulin resistance in mice with type 2 diabetes-like disease. Conversely, upregulation of p53 in adipose tissue caused an inflammatory response that led to insulin resistance. Adipose tissue from individuals with diabetes also showed senescence-like features. Our results show a previously unappreciated role of adipose tissue p53 expression in the regulation of insulin resistance and suggest that cellular aging signals in adipose tissue could be a new target for the treatment of diabetes., Cellular senescence was originally defined as the finite replication of human somatic cells in culture. As a consequence of semiconservative DNA replication, the ends of the chromosomes (telomeres) are not [...]

Published
2009

36. Mutations in CD96, a member of the immunoglobulin superfamily, cause a form of the C (optiz trigonocephaly) syndrome

Author

Kaname, Tadashi, Yoshiura, Ko-ichiro, Niikawa, Norio, Naritomi, Kenji, Kurosawa, Kenji, Fukushima, Bohring, Axel, Optiz, John M., Kubota, Yoshiaki, Oike, Yuichi, Yamamoto, Toshiyuki, Maehara, Hiroko, Own, Ichiro, Kanaya, Fuminori, Yanagi, Kumiko, Chinen, Yasutsugu, Makita, Yoshio, and Okamoto, Nobuhiko

Subjects
Gene mutations -- Research, Genetic research, Biological sciences
Abstract

An identification of a missense mutation in exon 6 of the CD96 gene in one patient with the C (opitz trigonocephaly) like syndrome. Result show CD96 mutations may cause a form of the C syndrome by interfering with cell adhesions and growth.

Published
2007

38. Angiopoietin-related growth factor antagonizes obesity and insulin resistance

Author

Oike, Yuichi, Akao, Masaki, Yasunaga, Kunio, Yamauchi, Toshimasa, Morisada, Tohru, Ito, Yasuhiro, Urano, Takashi, Kimura, Yoshishige, Kubota, Yoshiaki, Maekawa, Hiromitsu, Miyamoto, Takeshi, Miyata, Keishi, Matsumoto, Shun-ichiro, Sakai, Juro, Nakagata, Naomi, Takeya, Motohiro, Koseki, Haruhiko, Ogawa, Yoshihiro, Kadowaki, Takashi, and Suda, Toshio

Abstract

Angiopoietin-related growth factor (AGF), a member of the angiopoietin-like protein (Angptl) family, is secreted predominantly from the liver into the systemic circulation. Here, we show that most ( [greater than] 80%) of the AGF-deficient mice die at about embryonic day 13, whereas the surviving AGF-deficient mice develop marked obesity, lipid accumulation in skeletal muscle and liver, and insulin resistance accompanied by reduced energy expenditure relative to controls. In parallel, mice with targeted activation of AGF show leanness and increased insulin sensitivity resulting from increased energy expenditure. They are also protected from high-fat diet-induced obesity, insulin resistance and nonadipose tissue steatosis. Hepatic overexpression of AGF by adenoviral transduction, which leads to an approximately 2.5-fold increase in serum AGF concentrations, results in a significant (P [less than] 0.01) body weight loss and increases insulin sensitivity in mice fed a high-fat diet. This study establishes AGF as a new hepatocyte-derived circulating factor that counteracts obesity and related insulin resistance., Author(s): Yuichi Oike (corresponding author) [1]; Masaki Akao [1]; Kunio Yasunaga [2]; Toshimasa Yamauchi [3]; Tohru Morisada [1]; Yasuhiro Ito [1]; Takashi Urano [1]; Yoshishige Kimura [1]; Yoshiaki Kubota [1]; [...]

Published
2005
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44. Prostaglandin E2-EP4 Axis Promotes Lipolysis and Fibrosis in Adipose Tissue Leading to Ectopic Fat Deposition and Insulin Resistance

Author

Inazumi, Tomoaki, primary, Yamada, Kiyotaka, additional, Shirata, Naritoshi, additional, Sato, Hiroyasu, additional, Taketomi, Yoshitaka, additional, Morita, Kazunori, additional, Hohjoh, Hirofumi, additional, Tsuchiya, Soken, additional, Oniki, Kentaro, additional, Watanabe, Takehisa, additional, Sasaki, Yutaka, additional, Oike, Yuichi, additional, Ogata, Yasuhiro, additional, Saruwatari, Junji, additional, Murakami, Makoto, additional, and Sugimoto, Yukihiko, additional

Published
2020
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47. Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study

Author

Morinaga, Jun, primary, Kakuma, Tatsuyuki, additional, Fukami, Hirotaka, additional, Hayata, Manabu, additional, Uchimura, Kohei, additional, Mizumoto, Teruhiko, additional, Kakizoe, Yutaka, additional, Miyoshi, Taku, additional, Shiraishi, Naoki, additional, Adachi, Masataka, additional, Izumi, Yuichiro, additional, Kuwabara, Takashige, additional, Okadome, Yusuke, additional, Sato, Michio, additional, Horiguchi, Haruki, additional, Sugizaki, Taichi, additional, Kadomatsu, Tsuyoshi, additional, Miyata, Keishi, additional, Tajiri, Saeko, additional, Tajiri, Tetsuya, additional, Tomita, Kimio, additional, Kitamura, Kenichiro, additional, Oike, Yuichi, additional, and Mukoyama, Masashi, additional

Published
2019
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48. Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity

Author

Horiguchi, Haruki, primary, Kadomatsu, Tsuyoshi, additional, Kurahashi, Ryoma, additional, Hara, Chiaki, additional, Miyata, Keishi, additional, Baba, Masaya, additional, Osumi, Hironobu, additional, Terada, Kazutoyo, additional, Araki, Kimi, additional, Takai, Toshiyuki, additional, Kamba, Tomomi, additional, Linehan, W. Marston, additional, Moroishi, Toshiro, additional, and Oike, Yuichi, additional

Published
2019
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