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3 results on '"Hirohumi Utsumi"'

1. Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis

Author

Masahiro Yoshida, Shunsuke Minagawa, Jun Araya, Taro Sakamoto, Hiromichi Hara, Kazuya Tsubouchi, Yusuke Hosaka, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Nahoko Sato, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Hirohumi Utsumi, Hiroshi Wakui, Takanori Numata, Yumi Kaneko, Shohei Mori, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Takeo Iwamoto, Hirotaka Imai, and Kazuyoshi Kuwano

Subjects
Science
Abstract

Altered iron homeostasis resulting in excessive oxidative stress has been implicated in smoke-induced lung diseases. Here the authors show that ferroptosis of lung epithelial cells, potentially resulting from excessive ferritinophagy, is involved in the pathogenesis of COPD.

Published
2019
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2. Dasatinib-induced Nonspecific Interstitial Pneumonia That Developed 7 Years after the Initiation of Dasatinib

Author

Kazuyoshi Kuwano, Daisuke Takekoshi, Hirohumi Utsumi, Yoshinori Kawabata, Hiromichi Hara, Mitsuo Hashimoto, Jun Araya, Rei Makishima, Hiroshi Wakui, Masahiro Ikegami, Hanae Miyagawa, Takuya Akutsu, Junko Watanabe, Ayako Nishioka, Yuma Matsui, Yuki Noda, Takanori Numata, Shunsuke Minagawa, Ayu Kiritani, and Keitaro Okuda

Subjects
Male, medicine.medical_specialty, Non-specific interstitial pneumonia, Corticosteroid treatment, Dasatinib, Case Report, Lung biopsy, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, chronic myeloid leukemia, Internal medicine, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal Medicine, medicine, non-specific interstitial pneumonia, Humans, Interstitial pneumonia, Lung, Protein Kinase Inhibitors, interstitial lung disease, business.industry, Interstitial lung disease, Myeloid leukemia, General Medicine, respiratory system, Middle Aged, medicine.disease, respiratory tract diseases, 030211 gastroenterology & hepatology, business, Lung Diseases, Interstitial, Bosutinib, medicine.drug
Abstract

We report the case of a 56-year-old man with chronic myeloid leukemia (CML) who developed dasatinib-induced interstitial lung disease (ILD) 7 years after starting dasatinib, a BCR-ABL1 inhibitor. The patient presented with dyspnea. Chest imaging showed diffuse ground-glass opacities. A surgical lung biopsy showed cellular non-specific interstitial pneumonia (NSIP). Corticosteroid treatment ameliorated his condition. Bosutinib, another BCR-ABL1 inhibitor, was successfully re-instituted. The present case and relevant literature suggest that dasatinib-induced ILD can present as NSIP after an extended period, responds to corticosteroids, and is amenable to re-challenge at a lower-dose or with alternative BCR-ABL1 inhibitors.

Published
2020

3. Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis

Author

Tsukasa Kadota, Kenji Kobayashi, Yusuke Kurita, Saburo Ito, Katsutoshi Nakayama, Hiromichi Hara, Makoto Odaka, Takanori Numata, Hiroshi Wakui, Yumi Kaneko, Kazuya Tsubouchi, Shohei Mori, Akihiro Ichikawa, Makoto Yamashita, Yusuke Hosaka, Shunsuke Minagawa, Hirotaka Imai, Hisatoshi Asano, Kazuyoshi Kuwano, Nayuta Saito, Nahoko Sato, Masahiro Yoshida, Toshiaki Morikawa, Taro Sakamoto, Hirohumi Utsumi, Jun Araya, and Takeo Iwamoto

Subjects
0301 basic medicine, General Physics and Astronomy, 02 engineering and technology, GPX4, medicine.disease_cause, Pathogenesis, Lipid peroxidation, chemistry.chemical_compound, Pulmonary Disease, Chronic Obstructive, lcsh:Science, Phospholipids, COPD, Multidisciplinary, biology, Chronic obstructive pulmonary disease, Smoking, respiratory system, 021001 nanoscience & nanotechnology, Deferoxamine, 0210 nano-technology, medicine.drug, Cell death, Programmed cell death, Iron, Science, Nuclear Receptor Coactivators, Mice, Transgenic, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, Animals, Ferroptosis, Humans, business.industry, Epithelial Cells, General Chemistry, medicine.disease, respiratory tract diseases, Ferritin, Mice, Inbred C57BL, 030104 developmental biology, chemistry, biology.protein, Cancer research, lcsh:Q, Lipid Peroxidation, business, Reactive Oxygen Species, Oxidative stress
Abstract

Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions. Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis. Our in vivo and in vitro models show labile iron accumulation and enhanced lipid peroxidation with concomitant non-apoptotic cell death during cigarette smoke (CS) exposure, which are negatively regulated by GPx4 activity. Treatment with deferoxamine and ferrostatin-1, in addition to GPx4 knockdown, illuminate the role of ferroptosis in CS-treated lung epithelial cells. NCOA4-mediated ferritin selective autophagy (ferritinophagy) is initiated during ferritin degradation in response to CS treatment. CS exposure models, using both GPx4-deficient and overexpressing mice, clarify the pivotal role of GPx4-regulated cell death during COPD. These findings support a role for cigarette smoke-induced ferroptosis in the pathogenesis of COPD., Altered iron homeostasis resulting in excessive oxidative stress has been implicated in smoke-induced lung diseases. Here the authors show that ferroptosis of lung epithelial cells, potentially resulting from excessive ferritinophagy, is involved in the pathogenesis of COPD.

Published
2019

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