2015 Fiscal Year Annual Research Report
腸管免疫におけるセマフォリンシグナルを標的とした生活習慣病発症機序の解明
| Project/Area Number |
26670362
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
横手 幸太郎 千葉大学, 医学(系)研究科(研究院), 教授 (20312944)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
竹本 稔 千葉大学, 医学(系)研究科(研究院), 准教授 (60447307)
|
|---|
| Project Period (FY) |
2014-04-01 – 2016-03-31
|
| Keywords | 分泌蛋白 / 腸内細菌 / 腸管免疫 / 耐糖能 / インスリン感受性 / 脂肪肝 |
|---|
| Outline of Annual Research Achievements |
我々は血管内皮と腎ポドサイトに発現するSemaphorin3G(以下Sema3G)を同定し、このKOマウスを用いて腸内細菌叢ならびに高脂肪食負荷による代謝の変化を検討した。代表的な腸内細菌であるFirmicutes門およびBacteroides門の細菌量をリアルタイムPCRにて測定したところ、野生型においてはBacteroidesとFirmicutesは全菌種のそれぞれ25％程度を占めておりほぼ同等であった。一方、Sema3G KOではBacteroidesがFirmicutesに対し相対的に増加する傾向が見られた。平均のBacteroides/Firmicutes比は野生型1.05、ノックアウト1.30であり、有意差には至らなかった 。更に、メタゲノム解ではSema3G KOにおいては先述のBacteroidesとFirmicutesの変化とともに、Cyanobacteriaが増加、Verrucomicrobiaの減少がみられ、また、Bcteroides門の中ではBacteroidalesが増加し、Firmicutes門の中ではClostridialesの減少がみられた。また、高脂肪食負荷の影響を検討したが、KOマウスでは耐糖能が野生型に比較して高く、インスリン感受性がよく、脂肪肝が軽減される事が分かった。肝臓における炎症性サイトカインの発現も、KOマウスで減少する傾向があった。Sema3G KO マウスは野生型よりも普通食では体重増加する傾向があったが、高脂肪食であると明らかな体重の差は 見られなかった。以上より、Sema3Gは腸内細菌に影響している事、また高脂肪食下で脂肪肝を促進し、インスリン抵抗性を促進していると想定されるが、未だそのメカニズムは不明のままであり、今後もこの解明に取り組んでいく。
|
Research Products
(40 results)
-
[Journal Article] Cushing syndrome due to ACTH-secreting pheochromocytoma aggravated by a glucocorticoid-driven positive-feedback loop.2015
Author(s)
Sakuma I, Higuchi S, Fujimoto M, Takiguchi T, Nakayama A, Tamura A, Kohno T, Komai E, Shiga A, Nagano H, Hashimoto N, Suzuki S, Mayama T, Koide H, Ono K, Sasano H, Tatsuno I, Yokote K, Tanaka T.
-
Journal Title
J Clin Endocrinol Metab
Volume: 101(3)
Pages: 841-846
DOI
Open Access
-
-
[Journal Article] Unsuppressed lipolysis in adipocytes is linked with enhanced gluconeogenesis and altered bile acid physiology in Insr(P1195L/+) mice fed high-fat-diet.2015
Author(s)
Lee EY, Sakurai K, Zhang X, Toda C, Tanaka T, Jiang M, Shirasawa T, Tachibana K, Yokote K, Vidal-Puig A, Minokoshi Y, Miki T.
-
Journal Title
Sci Rep
Volume: 30
Pages: 5:17565
DOI
Open Access
-
[Journal Article] Pituitary adenylate cyclase-activating polypeptide protects glomerular podocytes from inflammatory injuries.2015
Author(s)
Sakamoto K, Kuno K, Takemoto M, He P, Ishikawa T, Onishi S, Ishibashi R, Okabe E, Shoji M, Hattori A, Yamaga M, Kobayashi K, Kawamura H, Tokuyama H, Maezawa Y, Yokote K.
-
Journal Title
J Diabetes Res
Volume: -
Pages: 727152
DOI
Open Access
-
[Journal Article] Comparison in decision-making between bulimia nervosa, anorexia nervosa, and healthy women: influence of mood status and pathological eating concerns.2015
Author(s)
Matsumoto J, Hirano Y, Numata N, Matzuzawa D, Murano S, Yokote K, Iyo M, Shimizu E, Nakazato M.
-
Journal Title
J Eat Disord.
Volume: 2
Pages: 3:14
DOI
Open Access
-
[Journal Article] Germline deletion of ARMC5 in familial primary macronodular adrenal hyperplasia.2015
Author(s)
Suzuki S, Tatsuno I, Oohara E, Nakayama A, Komai E, Shiga A, Kono T, Takiguchi T, Higuchi S, Sakuma I, Nagano H, Hashimoto N, Mayama T, Koide H, Sasano H, Nakatani Y, Imamoto T, Ichikawa T, Yokote K, Tanaka T.
-
Journal Title
Endocr Pract.
Volume: 21(10)
Pages: 1152-1160
DOI
Open Access
-
-
[Journal Article] Mitochondrial superoxide in osteocytes perturbs canalicular networks in the setting of age-related osteoporosis.2015
Author(s)
Kobayashi K, Nojiri H, Saita Y, Morikawa D, Ozawa Y, Watanabe K, Koike M, Asou Y, Shirasawa T, Yokote K, Kaneko K, Shimizu T.
-
Journal Title
Sci Rep.
Volume: 16
Pages: 5:9148
DOI
Open Access
-
[Journal Article] Mechanical overloading causes mitochondrial superoxide and SOD2 imbalance in chondrocytes resulting in cartilage degeneration.2015
Author(s)
Koike M, Nojiri H, Ozawa Y, Watanabe K, Muramatsu Y, Kaneko H, Morikawa D, Kobayashi K, Saita Y, Sasho T, Shirasawa T, Yokote K, Kaneko K, Shimizu T.
-
Journal Title
Sci Rep.
Volume: 25
Pages: 5:11722
DOI
Open Access
-
[Journal Article] Association of serum antibody levels against TUBB2C with diabetes and cerebral infarction.2015
Author(s)
Hiwasa T, Zhang XM, Kimura R, Machida T, Kitamura K, Yamazoe R, Kunimatsu M, Mine S, Kobayashi E, Iwadate Y, Saeki N, Takemoto M, Kobayashi K, Kawamura H, Ishibashi R, Sakurai K, Fujimoto M, Yokote K, Iwata Y, Nakayama T, Harada J, Kobayashi Y, Ohno M, Chen PM, Nishi E, Yokota M, Kamitsukasa I
-
Journal Title
Gratis J Biomed Sci,
Volume: 1(2)
Pages: 49-63
DOI
Open Access
-
[Journal Article] Identification of Cerebral Infarction-Specific Antibody Markers from Autoantibodies Detected in Patients with Systemic Lupus Erythematosus.2015
Author(s)
Goto K, Sugiyama T, Matsumura R, Zhang XM, Kimura R, Taira A, Arita E, Iwase K, Kobayashi E, Iwadate Y, Saeki N, Mori M, Uzawa A, Muto M, Kuwabara S, Takemoto M, Kobayashi K, Kawamura H, Ishibashi R, Sakurai K, Fujimoto, M, Yokote K, Nakayama T, Harada J, Kobayashi Y, Ohno M, Chin H
-
Journal Title
J Mol Biomark Diagnos
Volume: -
Pages: 6:2
DOI
Open Access
-
-
-
[Journal Article] Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with alpha-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on metformin or pioglitazone alone (Study for an Ultimate Combination Therapy to Control Diabetes with Sitagliptin-1): A multicenter, randomized, open-label, non-inferiority trial.2015
Author(s)
Yokoh H, Kobayashi K, Sato Y, Takemoto M, Uchida D, Kanatsuka A, Kuribayashi N, Terano T, Hashimoto N, Sakurai K, Hanaoka H, Ishikawa K, Onishi S, Yokote K.
-
Journal Title
J Diabetes Investig.
Volume: 6(2)
Pages: 182-191
DOI
Open Access
-
[Journal Article] Serum soluble LR11, a novel tumor derived biomarker associated with the outcome of patients with diffuse large B-cell lymphoma.2015
Author(s)
3.Ohwada C, Yamazaki A, Kawaguchi T, Sugita Y, Takeuchi M, Shimizu N, Sakaida E, Takeda Y, Tsukamoto S, Muto T, Jiang M, Higashi M, Yokote K, Tamaru JI, Bujo H, Nakaseko C.
-
Journal Title
Leuk Lymphoma.
Volume: 11
Pages: 2982-2985
DOI
Open Access
-
-
-
-
-
-
-
-
[Presentation] Novel approach to residual risk, K-877, a potent and selective PPAR-α Modulator(SPPARMα), added-on to Pitavastatin in Japanese patients with dyslipidemia.2015
Author(s)
Yokote K, Ishibashi S, Yamashita S, Arai H, Araki E, Suganami H, Kodama T.
Organizer
American Heart Association Scientific Session 2015
Place of Presentation
Orange County Convention Center(Orlando, USA.)
Year and Date
2015-11-09
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
