Does nonreceptor type tyrosine kinase Fyn participate in autophagy mechanism in diabetic nephropathy ?

• Project/Area Number: 15K09242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Gunma University
• Principal Investigator: Yamada Eijiro 群馬大学, 医学部附属病院, 助教 (60645563)
• Co-Investigator(Kenkyū-buntansha): 前嶋 明人 群馬大学, 大学院医学系研究科, 准教授 (70431707)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Fyn / Tgm2 / オートファジー / 糖尿病性腎症

Outline of Final Research Achievements

It was found that Fyn can directly phosphorylate Tgm2 in vitro. Wild type Tgm2 and phosphorylation site mutation Tgm2 were expressed in HK-2 cells, and the crosslinking of Beclin 1 was examined. It turned out that there was no change. When autophagy flux was examined in HK2 cells, autophagic activity was decreased in cells overexpressing Tgm2. This result seems to contribute to the elucidation of the mechanism of diabetic nephropathy.

Research Products

• [Journal Article] Serum sodium ion level influenced by daily salt intake after administration of sodium-glucose cotransporter 2 inhibitors. (2018)
  • Author(s): Yamada E, Osaki A, Saito T, Niijima Y, Okada J, Okada S, Yamada M.
  • Journal Title: Nutrition. Volume: 45 Pages: 146-146
  • DOI: 10.1016/j.nut.2017.05.008
  • Peer Reviewed
• [Journal Article] Postprandial serum C-peptide level is associated with increased urinary albumin-to-creatinine ratio in patients with type 2 diabetes mellitus (2017)
  • Author(s): Yamada Eijiro、Saito Tsugumichi、Niijima Yawara、Okada Shuichi、Yamada Masanobu
  • Journal Title: Clinical Nephrology Volume: 87 Issue: 06 Pages: 320-322
  • DOI: 10.5414/cn108978
  • Peer Reviewed
• [Journal Article] Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages. (2017)
  • Author(s): Tarabra E, An Lee TW, Zammit VA, Vatish M, Yamada E, Pessin JE, Bastie CC.
  • Journal Title: Oncotarget Volume: 49 Issue: 49 Pages: 86634-86645
  • DOI: 10.18632/oncotarget.21258
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elevated 1-h post-challenge glucose levels associated with increased arterial stiffness. (2017)
  • Author(s): Saito T, Niijima K, Yamada E, Niijima Y, Okada S, Yamada M.
  • Journal Title: J Diabetes. Volume: 1 Issue: 1 Pages: 102-103
  • DOI: 10.1111/1753-0407.12458
  • Peer Reviewed
• [Journal Article] HBA1C AND MEAN GLUCOSE DERIVED FROM SHORT-TERM CONTINUOUS GLUCOSE MONITORING ASSESSMENT DO NOT CORRELATE IN PATIENTS WITH HBA1C >8. (2017)
  • Author(s): Yamada E, Okada S, Nakajima Y, Bastie CC, Vatish M, Tagaya Y, Osaki A, Shimoda Y, Shibusawa R, Saito T, Okamura T, Ozawa A, Yamada M.
  • Journal Title: Endocr Pract. Volume: 1 Issue: 1 Pages: 10-16
  • DOI: 10.4158/ep161363.or
  • Peer Reviewed
• [Journal Article] Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations (2017)
  • Author(s): Okamura T, Nakajima Y, Katano-Toki A, Horiguchi K, Matsumoto S, Yoshino S, Yamada E, Tomaru T, Ishii S, Saito T, Ozawa A, Shibusawa N, Satoh T, Okada S, Nagaoka R, Takada D, Horiguchi J, Oyama T, Yamada M
  • Journal Title: Endocrine Journal Volume: 64 Issue: 1 Pages: 39-47
  • DOI: 10.1507/endocrj.EJ16-0243
  • NAID: 130005305975
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Insulin autoimmune syndrome during the administration of clopidogrel. (2016)
  • Author(s): Yamada E, Okada S, Saito T, Osaki A, Ozawa A, Yamada M.
  • Journal Title: J Diabetes. Volume: 4 Issue: 4 Pages: 588-589
  • DOI: 10.1111/1753-0407.12385
  • Peer Reviewed
• [Journal Article] Renal threshold for glucose reabsorption predicts diabetes improvement by sodium-glucose cotransporter 2 inhibitor therapy. (2016)
  • Author(s): Osaki A, Okada S, Saito T, Yamada E, Ono K, Niijima Y, Hoshi H, Yamada M.
  • Journal Title: J Diabetes Investig. Volume: 5 Issue: 5 Pages: 751-754
  • DOI: 10.1111/jdi.12473
  • Peer Reviewed / Open Access
• [Journal Article] APPL1 promotes glucose uptake in response to mechanical stretch via the PKCζ-non-muscle myosin IIa pathway in C2C12 myotubes. (2016)
  • Author(s): Saito T, Okada S, Shimoda Y, Tagaya Y, Osaki A, Yamada E, Shibusawa R, Nakajima Y, Ozawa A, Satoh T, Mori M, Yamada M
  • Journal Title: Cell Signal Volume: 28 Issue: 11 Pages: 1694-1702
  • DOI: 10.1016/j.cellsig.2016.07.010
  • Peer Reviewed / Open Access
• [Journal Article] Fyn phosphorylates AMPK to inhibit AMPK activity and AMP-dependent activation of autophagy. (2016)
  • Author(s): Yamada E, Okada S, Bastie CC, Vatish M, Nakajima Y, Shibusawa R, Ozawa A, Pessin JE, Yamada M.
  • Journal Title: Oncotarget Volume: 7 Issue: 46 Pages: 74612-74629
  • DOI: 10.18632/oncotarget.11916
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Subcutaneous abdominal adipose tissue is associated with an index of insulin sensitivity/resistance. (2016)
  • Author(s): Niijima K, Shimoda Y, Saito T, Yamada E, Niijima Y, Okada S, Yamada M.
  • Journal Title: Adipocyte. Volume: 5 Pages: 375-377
  • Peer Reviewed
• [Journal Article] GNAS mutations in adrenal aldosterone-producing adenomas [Rapid Communication] (2016)
  • Author(s): Nakajima Y, Okamura T, Horiguchi K, Gohko T, Miyamoto T, Satoh T, Ozawa A, Ishii S, Yamada E, Hashimoto K, Okada S, Takata D, Horiguchi J, Yamada M.
  • Journal Title: Endocrine Journal Volume: 63 Issue: 2 Pages: 199-204
  • DOI: 10.1507/endocrj.EJ15-0642
  • NAID: 130005127192
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Effect of dapagliflozin on colon cancer cell [Rapid Communication] (2015)
  • Author(s): Saito T, Okada S, Yamada E, Shimoda Y, Osaki A, Tagaya Y, Shibusawa R, Okada J, Yamada M.
  • Journal Title: Endocrine Journal Volume: 62 Issue: 12 Pages: 1133-1137
  • DOI: 10.1507/endocrj.EJ15-0396
  • NAID: 130005115205
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Fyn Activation of mTORC1 Stimulates the IRE1α-JNK Pathway, Leading to Cell Death. (2015)
  • Author(s): Wang Y, Yamada E, Zong H, Pessin JE.
  • Journal Title: J Biol Chem. Volume: 290(41) Issue: 41 Pages: 24772-83
  • DOI: 10.1074/jbc.m115.687020
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tctex1d2 Is a Negative Regulator of GLUT4 Translocation and Glucose Uptake. (2015)
  • Author(s): Shimoda Y, Okada S, Yamada E, Pessin JE, Yamada M.
  • Journal Title: Endocrinology. Volume: 156(10) Issue: 10 Pages: 3548-58
  • DOI: 10.1210/en.2015-1120
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 近位尿細管細胞株HK-2細胞における新たなオートファジー調節機構 (2017)
  • Author(s): 山田英二郎
  • Organizer: 第32回日本糖尿病合併症学会
• [Presentation] Identifying a new pathway to regulate AMPK activity under metabolic stress. (2016)
  • Author(s): 山田英二郎
  • Organizer: 11th IDF-WPR Congress 2016 & 8th AASD Scientific Meeting
  • Place of Presentation: Taipei International Convention Center (Taipei)
  • Year and Date: 2016-10-27
  • Int'l Joint Research
• [Presentation] 近位尿細管細胞株HK-2細胞における新たなオートファジー調節機構 (2016)
  • Author(s): 山田英二郎
  • Organizer: 第31回日本糖尿病合併症学会
  • Place of Presentation: 仙台国際センター（仙台）
  • Year and Date: 2016-10-07
• [Presentation] 3C(CSII,CGM,Carbocount)を利用したチーム医療のビルドアップとその効果 (2016)
  • Author(s): 山田英二郎
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2016-05-19
  • Invited
• [Presentation] メタボリックストレス状態においてFyn-AMPK経路はオートファジーを調節し得る。 (2016)
  • Author(s): 山田英二郎
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2016-05-19
• [Presentation] 当院におけるCSII導入前後の体重に対する影響に関しての検討 (2016)
  • Author(s): 山田英二郎
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2016-04-21
• [Presentation] Identifying a new pathway to regulate AMPK activity under metabolic stress. (2015)
  • Author(s): Eijiro Yamada
  • Organizer: 第75回アメリカ糖尿病学会
  • Place of Presentation: Boston Convention and Exhibition Center（ボストン）
  • Year and Date: 2015-06-05
  • Int'l Joint Research
• [Presentation] 長期TNFα刺激によるAMPキナーゼ調節機構の解明 (2015)
  • Author(s): 山田英二郎
  • Organizer: 第58回日本糖尿病学会学術集会
  • Place of Presentation: 海峡メッセ下関他（下関）
  • Year and Date: 2015-05-21
• [Presentation] 近位尿細管細胞株HK-2細胞におけるFynによる新たなオートファジー調節機構の解析 (2015)
  • Author(s): 山田英二郎
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ホテルニューオータニ東京（東京）
  • Year and Date: 2015-04-23