Takehiro Nakano

WCN26-5606 INDOXYL SULFATE DOWNREGULATES HEPATIC SEPP1 LEADING TO SELENIUM DEFICIENCY AND RENAL FERROPTOSIS

Yutaka Kitazato, Takehiro Nakano, Hitoshi Maeda, M Tanaka et autres

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Lactulose, a Disaccharide Prebiotic, Improves the Gut-Kidney Axis via Enhancement of Akkermansia Muciniphila Production

Miyu Sueyoshi, Hiroshi Watanabe, Moritaka Goto, Takao Sato et autres

KEY POINTS: Lactulose, a synthetic disaccharide, promotes Akkermansia muciniphila proliferation. The oral administration of both live and pasteurized forms of Akkermansia muciniphila significantly improved renal function in CKD-induced mice. Lactulose as a prebiotic therapeutic agent exerts the therapeutic effects on the gut-kidney …

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Efficacy of Nrf2 activation in a proteinuric Alport syndrome mouse model

Shota Kaseda, Jun Horizono, Yuya Sannomiya, Jun Kuwazuru et autres

Activation of nuclear factor erythroid 2–related factor 2 (Nrf2) has shown protective effects in experimental models of acute kidney injury and nonproteinuric chronic kidney disease. However, the efficacy of Nrf2 activation for proteinuric chronic kidney disease with glomerular injury is controversial, as …

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Indoxyl Sulfate Contributes to Selenium Deficiency and Renal Ferroptosis by Decreasing the Expression of Selenium Transport Protein Selenoprotein P

Takehiro Nakano, Yutaka Kitazato, Kai Tokumaru, Yuhi Shintani et autres

Key Points Indoxyl sulfate (IS) is involved in the liver-kidney axis by inducing renal ferroptosis by selenium deficiency due to suppression of selenoprotein P (SEPP1) expression in the liver. IS concentrations were negatively associated with selenium concentrations and SEPP1 concentrations in serum …

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尿毒症物質が誘発する腎病態進展の分子基盤に関する研究

Takehiro Nakano

Kidney Protection by a Novel Keap1-Nrf2 Protein-Protein Interaction Inhibitor for a Mouse Model of Alport Syndrome

Jun Horizono, Shota Kaseda, Yuya Sannomiya, Mary Ann Suico et autres

Background: Keap1-Nrf2 pathway plays an important role in the defense mechanism against oxidative stress in the kidney. We have shown that UBE-1099, a Keap1-Nrf2 protein-protein interaction (PPI) inhibitor, exerts renoprotective effects in Alport syndrome (AS) mice (Kidney 360, 2022). Furthermore, we found …

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The Uremic Toxin Indoxyl Sulfate Contributes to Renal Fibrosis via mTORC1 Signaling Pathway

Takehiro Nakano, Hiroshi Watanabe, Toru Maruyama

Background: Activation of mTORC1 in renal tissue has been reported in chronic kidney disease (CKD)-induced renal fibrosis. This suggests that the regulation of renal mTORC1 activity represents a potential therapeutic target for the treatment of renal fibrosis. However, the molecular mechanisms responsible …

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Therapeutic Effects of Albumin-Fused BMP7 on 2 Experimental Models of Liver Fibrosis

Mei Takano, Hiroshi Watanabe, Shota Toda, Kento Nishida et autres

Despite the fact that liver fibrosis is an intractable disease with a poor prognosis, effective therapeutic agents are not available. In this study, we focused on bone morphogenetic factor 7 (BMP7) that inhibits transforming growth factor (TGF)-β signaling, which is involved in …

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Advanced Oxidation Protein Products Contribute to Chronic-Kidney-Disease-Induced Adipose Inflammation through Macrophage Activation

Nanaka Arimura, Hiroshi Watanabe, Hiromasa Kato, Tadashi Imafuku et autres

Fat atrophy and adipose tissue inflammation can cause the pathogenesis of metabolic symptoms in chronic kidney disease (CKD). During CKD, the serum levels of advanced oxidation protein products (AOPPs) are elevated. However, the relationship between fat atrophy/adipose tissue inflammation and AOPPs has …

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Indoxyl Sulfate Contributes to mTORC1-Induced Renal Fibrosis via The OAT/NADPH Oxidase/ROS Pathway

Takehiro Nakano, Hiroshi Watanabe, Tadashi Imafuku, Kai Tokumaru et autres

Activation of mTORC1 (mechanistic target of rapamycin complex 1) in renal tissue has been reported in chronic kidney disease (CKD)-induced renal fibrosis. However, the molecular mechanisms responsible for activating mTORC1 in CKD pathology are not well understood. The purpose of this study …

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Advanced oxidation protein products contribute to chronic kidney disease‐induced muscle atrophy by inducing oxidative stress via CD36/NADPH oxidase pathway

Hiromasa Kato, Hiroshi Watanabe, Tadashi Imafuku, Nanaka Arimura et autres

Abstract Background Sarcopenia with chronic kidney disease (CKD) progression is associated with life prognosis. Oxidative stress has attracted interest as a trigger for causing CKD‐related muscular atrophy. Advanced oxidation protein products (AOPPs), a uraemic toxin, are known to increase oxidative stress. However, …

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Cysteinylated Albumin as a Potential Biomarker for the Progression of Kidney Disease in Patients With Type 2 Diabetes

Tadashi Imafuku, Hiroshi Watanabe, Kentaro Oniki, Akira Yoshida et autres

Currently, the gold standard for diagnosing diabetic kidney disease (DKD) is the measurement of the urinary albumin-to-creatinine ratio (UACR), but it has been clarified that there are many cases of decreased renal function and atypical nephropathy without the development of albuminuria (1,2). …

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