研究成果Report

• 腎臓内科学
• 神経内科学
• 循環器内科学
• 消化器内科学
• 内分泌内科学
• 免疫内科学
• 皮膚科学
• 小児科学
• 眼科学
• 吉森研究室

 

腎臓内科学

Matsui S, Yamamoto T, Takabatake Y, Takahashi A, Namba-Hamano T, Matsuda J, Minami S, Sakai S, Yonishi H, Nakamura J, Kawai H, Kubota T, Matsui I, Yanagita M, Isaka Y. Defective autophagy and AMPK inactivation drive ferroptosis in diabetic kidney disease. Diabetologia. 2026; 69(3): 815-832.

Yamamoto T, Minami S, Isaka Y. Autophagy in kidney physiology: from cellular quality control to organ metabolism. Autophagy Rep. 2026; 5(1): 2622228.

Yamamoto T. Autophagic stagnation: a key mechanism in kidney disease progression linked to aging and obesity．Clin Exp Nephrol. 2025; 29(6): 711-719.

Matsui S, Yamamoto T, Takabatake Y, Takahashi A, Namba-Hamano T, Matsuda J, Minami S, Sakai S, Yonishi H, Nakamura J, Maeda S, Matsumoto A, Matsui I, Yanagita M, Isaka Y. Empagliflozin protects the kidney by reducing toxic ALB (albumin) exposure and preventing autophagic stagnation in proximal tubules. Autophagy. 2025; 21(3): 583-597.

Nakamura J, Yamamoto T, Takabatake Y, Namba-Hamano T, Takahashi A, Matsuda J, Minami S, Sakai S, Yonishi H, Maeda S, Matsui S, Kawai H, Matsui I, Yamamuro T, Edahiro R, Takashima S, Takasawa A, Okada Y, Yoshimori T, Ballabio A, Isaka Y. Age-related TFEB downregulation in proximal tubules causes systemic metabolic disorders and occasional apolipoprotein A4-related amyloidosis. JCI Insight. 2024; 10(3): e184451.

Maeda S, Sakai S, Takabatake Y, Yamamoto T, Minami S, Nakamura J, Namba-Hamano T, Takahashi A, Matsuda J, Yonishi H, Matsui S, Imai A, Edahiro R, Yamamoto-Imoto H, Matsui I, Takashima S, Imamura R, Nonomura N, Yanagita M, Okada Y, Ballabio A, Nakamura S, Yoshimori T, Isaka Y. MondoA and AKI and AKI-to-CKD Transition. J Am Soc Nephrol. 2024; 35(9): 1164-82.

Cui M, Yamano K, Yamamoto K, Yamamoto-Imoto H, Minami S, Yamamoto T, Matsui S, Kaminishi T, Shima T, Ogura M, Tsuchiya M, Nishino K, Layden BT, Kato H, Ogawa H, Oki S, Okada Y, Isaka Y, Kosako H, Matsuda N, Yoshimori T, Nakamura S. HKDC1, a target of TFEB, is essential to maintain both mitochondrial and lysosomal homeostasis, preventing cellular senescence. Proc Natl Acad Sci U S A. 2024; 121(2): e2306454120.

Minami S, Sakai S, Yamamoto T, Takabatake Y, Namba-Hamano T, Takahashi A, Matsuda J, Yonishi H, Nakamura J, Maeda S, Matsui S, Matsui I, Isaka Y. FGF21 and autophagy coordinately counteract kidney disease progression during aging and obesity. Autophagy. 2024; 20(3): 489-504.

Ogura M, Kaminishi T, Shima T, Torigata M, Bekku N, Tabata K, Minami S, Nishino K, Nezu A, Hamasaki M, Kosako H, Yoshimori T, Nakamura S. Microautophagy regulated by STK38 and GABARAPs is essential to repair lysosomes and prevent aging. EMBO Rep. 2023; 24(12): e57300.

Nakamura J, Yamamoto T, Takabatake Y, Namba-Hamano T, Minami S, Takahashi A, Matsuda J, Sakai S, Yonishi H, Maeda S, Matsui S, Matsui I, Hamano T, Takahashi M, Goto M, Izumi Y, Bamba T, Sasai M, Yamamoto M, Matsusaka T, Niimura F, Yanagita M, Nakamura S, Yoshimori T, Ballabio A, Isaka Y. TFEB-mediated lysosomal exocytosis alleviates high-fat diet-induced lipotoxicity in the kidney. JCI Insight. 2023; 8(4): e162498.

Yamamoto-Imoto H, Minami S, Shioda T, Yamashita Y, Sakai S, Maeda S, Yamamoto T, Oki S, Takashima M, Yamamuro T, Yanagawa K, Edahiro R, Iwatani M, So M, Tokumura A, Abe T, Imamura R, Nonomura N, Okada Y, Ayer DE, Ogawa H, Hara E, Takabatake Y, Isaka Y, Nakamura S, Yoshimori T. Age-associated decline of MondoA drives cellular senescence through impaired autophagy and mitochondrial homeostasis. Cell Rep. 2022; 38(9): 110444.

9Fujita T, Kubo S, Shioda T, Tokumura A, Minami S, Tsuchiya M, Isaka Y, Ogawa H, Hamasaki M, Yu L, Yoshimori T, Nakamura S. THOC4 regulates energy homeostasis by stabilizing TFEB mRNA during prolonged starvation. J Cell Sci. 2021; 134(6): jcs248203.

Yamamoto T, Takabatake Y, Minami S, Sakai S, Fujimura R, Takahashi A, Namba-Hamano T, Matsuda J, Kimura T, Matsui I, Kaimori JY, Takeda H, Takahashi M, Izumi Y, Bamba T, Matsusaka T, Niimura F, Yanagita M, Isaka Y. Eicosapentaenoic acid attenuates renal lipotoxicity by restoring autophagic flux. Autophagy. 2021; 17(7): 1700-1713.

 

神経内科学

Aguirre C, Miyanoiri Y, So M, Tamaki H, Maruno T, Doi J, Wang N, Yamaguchi K, Nakajima K, Yamamori Y, Inoura H, Choong CJ, Kakuda K, Ajiki T, Kimura Y, Ozono T, Baba K, Nagano S, Nagai Y, Ogi H, Uchiyama S, Matsuki Y, Tomii K, Goto Y, Ikenaka K, Mochizuki H. Conformational Switch in the Alpha-Synuclein C-Terminal Domain Directs Its Fibril Polymorphs．Chemistry. 2025; 31(37): e202500650.

Kakuda K, Ikenaka K, Kuma A, Doi J, Aguirre C, Wang N, Ajiki T, Choong CJ, Kimura Y, Badawy SMM, Shima T, Nakamura S, Baba K, Nagano S, Nagai Y, Yoshimori T, Mochizuki H. Lysophagy protects against propagation of α-synuclein aggregation through ruptured lysosomal vesicles. Proc Natl Acad Sci U S A. 2024; 121(1): e2312306120.

Zhou L, Hajiri T, Nakajima K, Aguirre C, Ikenaka K, Mochizuki H, Yamaguchi K, Goto Y, Ogi H. Ultrastiff Amyloid-Fibril Network of α-Synuclein Formed by Surface Seeding Reaction Confirmed by Multichannel Electrodeless Quartz-Crystal-Microbalance Biosensor. ACS Sens. 2023; 8(7): 2598-2608.

Choong CJ, Okuno T, Ikenaka K, Baba K, Hayakawa H, Koike M, Yokota M, Doi J, Kakuda K, Takeuchi T, Kuma A, Nakamura S, Nagai Y, Nagano S, Yoshimori T, Mochizuki H. Alternative mitochondrial quality control mediated by extracellular release. Autophagy. 2021; 17(10): 2962-2974.

Oe Y, Kakuda K, Yoshimura SI, Hara N, Hasegawa J, Terawaki S, Kimura Y, Ikenaka K, Suetsugu S, Mochizuki H, Yoshimori T, Nakamura S. PACSIN1 is indispensable for amphisome-lysosome fusion during basal autophagy and subsets of selective autophagy. PLoS Genet. 2022; 18(6): e1010264.

 

循環器内科学

Sugihara R, Taneike M, Murakawa T, Tamai T, Ueda H, Kitazume-Taneike R, Oka T, Akazawa Y, Nishida H, Mine K, Hioki A, Omi J, Omiya S, Aoki J, Ikeda K, Nishida K, Arita M, Yamaguchi O, Sakata Y, Otsu K. Lysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34. Nat Commun. 2023; 14(1): 4494.

Kameda S, Higo S, Shiba M, Kondo T, Li J, Liu L, Tabata T, Inoue H, Okuno S, Ogawa S, Kuramoto Y, Yasutake H, Lee JK, Takashima S, Ikeda Y, Hikoso S, Miyagawa S, Sakata Y. Modeling Reduced Contractility and Stiffness Using iPSC-Derived Cardiomyocytes Generated From Female Becker Muscular Dystrophy Carrier. JACC Basic Transl Sci. 2023; 8(6): 599-613.

Akazawa Y, Taneike M, Ueda H, Kitazume-Taneike R, Murakawa T, Sugihara R, Yorifuji H, Nishida H, Mine K, Hioki A, Omiya S, Nakayama H, Yamaguchi O, Yoshimori T, Sakata Y, Otsu K. Rubicon-regulated beta-1 adrenergic receptor recycling protects the heart from pressure overload. Sci Rep. 2022; 12(1): 41.

 

消化器内科学

Fukumoto K, Hikita H, Saito Y, Makino Y, Soma K, Kato S, Sasaki Y, Myojin Y, Sato K, Sakane S, Murai K, Tahata Y, Kodama T, Tatsumi T, Motooka D, Kubota Y, Kobayashi S, Eguchi H, Takehara T. Liver Sinusoidal Endothelial Cells Promote Metabolic Dysfunction-associated Steatohepatitis Progression via Interleukin-1R1-mediated Chemokine Production Induced by Macrophage-derived Interleukin-1β. Cell Mol Gastroenterol Hepatol. 2025; 20(4): 101698.

Inoue T, Hayashi Y, Tsujii Y, Yoshii S, Sakatani A, Kimura K, Uema R, Kato M, Saiki H, Shinzaki S, Iijima H, Takehara T. Suppression of autophagy promotes fibroblast activation in p53-deficient colorectal cancer cells. Sci Rep. 2021; 11(1): 19524.

Sakane S, Hikita H, Shirai K, Myojin Y, Sasaki Y, Kudo S, Fukumoto K, Mizutani N, Tahata Y, Makino Y, Yamada R, Kodama T, Sakamori R, Tatsumi T, Takehara T. White Adipose Tissue Autophagy and Adipose-Liver Crosstalk Exacerbate Nonalcoholic Fatty Liver Disease in Mice. Cell Mol Gastroenterol Hepatol. 2021; 12(5): 1683-1699.

Myojin Y, Hikita H, Sugiyama M, Sasaki Y, Fukumoto K, Sakane S, Makino Y, Takemura N, Yamada R, Shigekawa M, Kodama T, Sakamori R, Kobayashi S, Tatsumi T, Suemizu H, Eguchi H, Kokudo N, Mizokami M, Takehara T. Hepatic Stellate Cells in Hepatocellular Carcinoma Promote Tumor Growth Via Growth Differentiation Factor 15 Production. Gastroenterology. 2021; 160(5): 1741-1754.e16.

 

内分泌内科学

Kondo Y, Fukuda S, Kawada K, Kita S, Nakamura Y, Nagao H, Obata Y, Fujishima Y, Maeda N, Nishizawa H, Shimomura I. Soluble T-cadherin ameliorates pressure overload-induced heart failure and cardiac fibrosis in mice. Biochem Biophys Res Commun. 2025; 779: 152459.

Fukuoka K, Mineo R, Kita S, Fukuda S, Okita T, Kawada-Horitani E, Iioka M, Fujii K, Kawada K, Fujishima Y, Nishizawa H, Norikazu M, Shimomura I. ER stress decreases exosome production through adiponectin/T-cadherin-dependent and -independent pathways. J Biol Chem. 2023; 299(9): 105114.

Kawada K, Kita S, Fukuda S, Fukuoka K, Okita T, Kawada-Horitani E, Iioka M, Sakaue TA, Kawachi Y, Fujii K, Kimura Y, Otabe S, Fujishima Y, Nishizawa H, Maeda N, Shimomura I. Chronic hyperadiponectinemia induced by transgenic overexpression increases plasma exosomes without significantly improving glucose and lipid metabolism. Endocr J. 2023; 70(6): 635-645.

Tsugawa-Shimizu Y, Fujishima Y, Kita S, Minami S, Sakaue TA, Nakamura Y, Okita T, Kawachi Y, Fukuda S, Namba-Hamano T, Takabatake Y, Isaka Y, Nishizawa H, Ranscht B, Maeda N, Shimomura I. Increased vascular permeability and severe renal tubular damage after ischemia-reperfusion injury in mice lacking adiponectin or T-cadherin. Am J Physiol Endocrinol Metab. 2021; 320(2): E179-E190.

 

免疫内科学

Tsujimoto K, Jo T, Nagira D, Konaka H, Park JH, Yoshimura SI, Ninomiya A, Sugihara F, Hirayama T, Itotagawa E, Matsuzaki Y, Takaichi Y, Aoki W, Saita S, Nakamura S, Ballabio A, Nada S, Okada M, Takamatsu H, Kumanogoh A. The lysosomal Ragulator complex activates NLRP3 inflammasome in vivo via HDAC6. EMBO J. 2023; 42(1): e111389.

Yoshida G, Kawabata T, Takamatsu H, Saita S, Nakamura S, Nishikawa K, Fujiwara M, Enokidani Y, Yamamuro T, Tabata K, Hamasaki M, Ishii M, Kumanogoh A, Yoshimori T. Degradation of the NOTCH intracellular domain by elevated autophagy in osteoblasts promotes osteoblast differentiation and alleviates osteoporosis. Autophagy. 2022; 18(10): 2323-2332.

 

皮膚科学

Takiguchi K, Yokoi K, Murase D, Yokota M, Kawabata K, Takahashi Y, Minami S, Nakamura S, Yoshimori T, Watanabe R, Fujimoto M, Tanemura A. Significant Role of Autophagy in Melanosomal Degradation of Dermal Macrophages: Therapeutic Insight Regarding Hyperpigmentation with Uncertain Etiology. J Invest Dermatol. 2024; S0022-202X(24)02151-1.

Matsumura Y, Watanabe R, Koguchi-Yoshioka H, Kume M, Nakai S, Furuta J, Azukizawa H, Ishitsuka Y, Tanemura A, Taminato M, Tashima H, Otani N, Tomita K, Kubo T, Fujimoto M. Possible Plasticity of Cytotoxic Resident Memory T Cells in Fixed Drug Eruption. J Invest Dermatol. 2023; 143(6): 1097-1100.e8.

Matsumura Y, Watanabe R, Koguchi-Yoshioka H, Nakamura Y, Saito A, Kume M, Nakai S, Ishitsuka Y, Furuta J, Fujimoto M. IL-10‒Producing Potency from Blood B Cells Correlates with the Prognosis of Alopecia Areata. J Invest Dermatol. 2023; 143(5): 871-874.e5.

Takahashi A, Hattori S, Sakai E, Yang L, Katayama I, Fujimoto M, Wataya-Kaneda M. Distribution of hypomelanotic macules in tuberous sclerosis complex: A retrospective cohort study. J Am Acad Dermatol. 2022; 87(1): 237-240.

 

小児科学

Kawatani K, Nambara T, Nawa N, Yoshimatsu H, Kusakabe H, Hirata K, Tanave A, Sumiyama K, Banno K, Taniguchi H, Arahori H, Ozono K, Kitabatake Y. A human isogenic iPSC-derived cell line panel identifies major regulators of aberrant astrocyte proliferation in Down syndrome. Commun Biol. 2021; 4(1): 730.

Hirata K, Nambara T, Kawatani K, Nawa N, Yoshimatsu H, Kusakabe H, Banno K, Nishimura K, Ohtaka M, Nakanishi M, Taniguchi H, Arahori H, Wada K, Ozono K, Kitabatake Y. 4-Phenylbutyrate ameliorates apoptotic neural cell death in Down syndrome by reducing protein aggregates. Sci Rep. 2020; 10(1):14047.

Nawa N, Hirata K, Kawatani K, Nambara T, Omori S, Banno K, Kokubu C, Takeda J, Nishimura K, Ohtaka M, Nakanishi M, Okuzaki D, Taniguchi H, Arahori H, Wada K, Kitabatake Y, Ozono K. Elimination of Protein Aggregates Prevents Premature Senescence in Human Trisomy 21 Fibroblasts. PLOS ONE 2019; 14(7): e0219592.

 

眼科学

Ando S, Hashida N, Yamashita D, Kawabata T, Asao K, Kawasaki S, Sakurai K, Yoshimori T, Nishida K. Rubicon regulates A2E-induced autophagy impairment in the retinal pigment epithelium implicated in the pathology of age-related macular degeneration. Biochem Biophys Res Commun. 2021; 551: 148-154.

 

吉森研究室

Yanagawa K, Kuma A, Hamasaki M, Kita S, Yamamuro T, Nishino K, Nakamura S, Omori H, Kaminishi T, Oikawa S, Kato Y, Edahiro R, Kawagoe R, Taniguchi T, Tanaka Y, Shima T, Tabata K, Iwatani M, Bekku N, Hanayama R, Okada Y, Akimoto T, Kosako H, Takahashi A, Shimomura I, Sakata Y, Yoshimori T. Nat Cell Biol. 2024; 26(9): 1558-1570.

Tabata K, Imai K, Fukuda K, Yamamoto K, Kunugi H, Fujita T, Kaminishi T, Tischer C, Neumann B, Reither S, Verissimo F, Pepperkok R, Yoshimori T, Hamasaki M. Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy. Nat Commun. 2024; 15(1): 7194.

Kitta S, Kaminishi T, Higashi M, Shima T, Nishino K, Nakamura N, Kosako H, Yoshimori T, Kuma A. YIPF3 and YIPF4 regulate autophagic turnover of the Golgi apparatus. EMBO J. 2024; 43(14): 2954-2978.

Cui M, Yamano K, Yamamoto K, Yamamoto-Imoto H, Minami S, Yamamoto T, Matsui S, Kaminishi T, Shima T, Ogura M, Tsuchiya M, Nishino K, Layden BT, Kato H, Ogawa H, Oki S, Okada Y, Isaka Y, Kosako H, Matsuda N, Yoshimori T, Nakamura S. HKDC1, a target of TFEB, is essential to maintain both mitochondrial and lysosomal homeostasis, preventing cellular senescence. Proc Natl Acad Sci U S A. 2024; 121(2): e2306454120.

Ogura M, Kaminishi T, Shima T, Torigata M, Bekku N, Tabata K, Minami S, Nishino K, Nezu A, Hamasaki M, Kosako H, Yoshimori T, Nakamura S. Microautophagy regulated by STK38 and GABARAPs is essential to repair lysosomes and prevent aging. EMBO Rep. 2023; 24(12): e57300.

Shioda T, Takahashi I, Ikenaka K, Fujita N, Kanki T, Oka T, Mochizuki H, Antebi A, Yoshimori T, Nakamura S. Neuronal MML-1/MXL-2 regulates systemic aging via glutamate transporter and cell nonautonomous autophagic and peroxidase activity. Proc Natl Acad Sci U S A. 2023; 120(39): e2221553120.

Shima T, Ogura M, Matsuda R, Nakamura S, Jin N, Yoshimori T, Kuma A. The TMEM192-mKeima probe specifically assays lysophagy and reveals its initial steps. J Cell Biol. 2023; 222(12): e202204048.

Nakamura S, Shigeyama S, Minami S, Shima T, Akayama S, Matsuda T, Esposito A, Napolitano G, Kuma A, Namba-Hamano T, Nakamura J, Yamamoto K, Sasai M, Tokumura A, Miyamoto M, Oe Y, Fujita T, Terawaki S, Takahashi A, Hamasaki M, Yamamoto M, Okada Y, Komatsu M, Nagai T, Takabatake Y, Xu H, Isaka Y, Ballabio A, Yoshimori T. LC3 lipidation is essential for TFEB activation during the lysosomal damage response to kidney injury. Nat Cell Biol. 2020; 22(10): 1252-1263.

Yamamuro T, Kawabata T, Fukuhara A, Saita S, Nakamura S, Takeshita H, Fujiwara M, Enokidani Y, Yoshida G, Tabata K, Hamasaki M, Kuma A, Yamamoto K, Shimomura I, Yoshimori T. Age-dependent loss of adipose Rubicon promotes metabolic disorders via excess autophagy. Nat Commun. 2020; 11(1): 4150.