九州大学 研究者情報
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松下 克之(まつした かつゆき) データ更新日:2022.06.09



主な研究テーマ
急性腎障害の慢性腎臓病への移行に関する基礎的研究
キーワード:急性腎障害、慢性腎臓病
2017.03.
ケモカインおよびグリア細胞と神経障害性疼痛に関する基礎的研究

キーワード:ケモカイン、神経障害性疼痛、グリア細胞
2012.04~2016.03.
心肺蘇生後の長期脳機能障害、腎障害に関する基礎的研究
キーワード:心肺停止、心肺蘇生、急性腎障害、脳機能障害
2017.03.
研究業績
主要著書
主要原著論文
1. Katsuyuki Matsushita, Kiyoshi Mori, Turgay Saritas, Mahaba B Eiwaz, Yoshio Funahashi, Megan N Nickerson, Jessica F Hebert, Adam C Munhall, James A McCormick, Motoko Yanagita, Michael P Hutchens, Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Mice., Journal of the American Society of Nephrology : JASN, 10.1681/ASN.2020030263, 32, 10, 2579-2594, 2021.10, BACKGROUND: Rhabdomyolysis, the destruction of skeletal muscle, is a significant cause of AKI and death in the context of natural disaster and armed conflict. Rhabdomyolysis may also initiate CKD. Development of specific pharmacologic therapy is desirable because supportive care is nearly impossible in austere environments. Myoglobin, the principal cause of rhabdomyolysis-related AKI, undergoes megalin-mediated endocytosis in proximal tubule cells, a process that specifically injures these cells. METHODS: To investigate whether megalin is protective in a mouse model of rhabdomyolysis-induced AKI, we used male C57BL/6 mice and mice (14-32 weeks old) with proximal tubule-specific deletion of megalin. We used a well-characterized rhabdomyolysis model, injection of 50% glycerol in normal saline preceded by water deprivation. RESULTS: Inducible proximal tubule-specific deletion of megalin was highly protective in this mouse model of rhabdomyolysis-induced AKI. The megalin knockout mice demonstrated preserved GFR, reduced proximal tubule injury (as indicated by kidney injury molecule-1), and reduced renal apoptosis 24 hours after injury. These effects were accompanied by increased urinary myoglobin clearance. Unlike littermate controls, the megalin-deficient mice also did not develop progressive GFR decline and persistent new proteinuria. Administration of the pharmacologic megalin inhibitor cilastatin to wild-type mice recapitulated the renoprotective effects of megalin deletion. This cilastatin-mediated renoprotective effect was dependent on megalin. Cilastatin administration caused selective proteinuria and inhibition of tubular myoglobin uptake similar to that caused by megalin deletion. CONCLUSIONS: We conclude that megalin plays a critical role in rhabdomyolysis-induced AKI, and megalin interference and inhibition ameliorate rhabdomyolysis-induced AKI. Further investigation of megalin inhibition may inform translational investigation of a novel potential therapy..
2. Katsuyuki Matsushita, Turgay Saritas, Mahaba B Eiwaz, Nicholas McClellan, Ian Coe, Wenbin Zhu, Mohammed Z Ferdaus, Lynn Y Sakai, James A McCormick, Michael P Hutchens, The acute kidney injury to chronic kidney disease transition in a mouse model of acute cardiorenal syndrome emphasizes the role of inflammation., Kidney international, 10.1016/j.kint.2019.06.022, 97, 1, 95-105, 2020.01, Acute cardiorenal syndrome is a common complication of acute cardiovascular disease. Studies of acute kidney injury (AKI) to chronic kidney disease (CKD) transition, including patients suffering acute cardiovascular disease, report high rates of CKD development. Therefore, acute cardiorenal syndrome associates with CKD, but no study has established causation. To define this we used a murine cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) model or sham procedure on male mice. CA was induced with potassium chloride while CPR consisted of chest compressions and epinephrine eight minutes later. Two weeks after AKI was induced by CA/CPR, the measured glomerular filtration rate (GFR) was not different from sham. However, after seven weeks the mice developed CKD, recapitulating clinical observations. One day, and one, two, and seven weeks after CA/CPR, the GFR was measured, and renal tissue sections were evaluated for various indices of injury and inflammation. One day after CA/CPR, acute cardiorenal syndrome was indicated by a significant reduction of the mean GFR (649 in sham, vs. 25 μL/min/100g in CA/CPR animals), KIM-1 positive tubules, and acute tubular necrosis. Renal inflammation developed, with F4/80 positive and CD3-positive cells infiltrating the kidney one day and one week after CA/CPR, respectively. Although there was functional recovery with normalization of GFR two weeks after CA/CPR, deposition of tubulointerstitial matrix proteins α-smooth muscle actin and fibrillin-1 progressed, along with a significantly reduced mean GFR (623 in sham vs. 409 μL/min/100g in CA/CPR animals), proteinuria, increased tissue transforming growth factor-β, and fibrosis establishing the development of CKD seven weeks after CA/CPR. Thus, murine CA/CPR, a model of acute cardiorenal syndrome, causes an AKI-CKD transition likely due to prolonged renal inflammation..
3. Rumie Wakasaki, Katsuyuki Matsushita, Kirsti Golgotiu, Sharon Anderson, Mahaba B Eiwaz, Daniel J Orton, Sang Jun Han, H Thomas Lee, Richard D Smith, Karin D Rodland, Paul D Piehowski, Michael P Hutchens, Glomerular filtrate proteins in acute cardiorenal syndrome., JCI insight, 10.1172/jci.insight.122130, 4, 4, 2019.02, Acute cardiorenal syndrome (CRS-1) is a morbid complication of acute cardiovascular disease. Heart-to-kidney signals transmitted by "cardiorenal connectors" have been postulated, but investigation into CRS-1 has been limited by technical limitations and a paucity of models. To address these limitations, we developed a translational model of CRS-1, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), and now report findings from nanoscale mass spectrometry proteomic exploration of glomerular filtrate 2 hours after CA/CPR or sham procedure. Filtrate acquisition was confirmed by imaging, molecular weight and charge distribution, and exclusion of protein specific to surrounding cells. Filtration of proteins specific to the heart was detected following CA/CPR and confirmed with mass spectrometry performed using urine collections from mice with deficient tubular endocytosis. Cardiac LIM protein was a CA/CPR-specific filtrate component. Cardiac arrest induced plasma release of cardiac LIM protein in mice and critically ill human cardiac arrest survivors, and administration of recombinant cardiac LIM protein to mice altered renal function. These findings demonstrate that glomerular filtrate is accessible to nanoscale proteomics and elucidate the population of proteins filtered 2 hours after CA/CPR. The identification of cardiac-specific proteins in renal filtrate suggests a novel signaling mechanism in CRS-1. We expect these findings to advance understanding of CRS-1..
4. Katsuyuki Matsushita, Hidetoshi Tozaki-Saitoh, Chinami Kojima, Takahiro Masuda, Makoto Tsuda, Kazuhide Inoue, Sumio Hoka, Chemokine (C-C motif) receptor 5 is an important pathological regulator in the development and maintenance of neuropathic pain., Anesthesiology, 10.1097/ALN.0000000000000190, 120, 6, 1491-503, 2014.06, BACKGROUND: The chemokine family has been revealed to be involved in the pathogenesis of neuropathic pain. In this study, the authors investigated the role of chemokine (C-C motif) ligand 3 and its receptors chemokine (C-C motif) receptor 1 and chemokine (C-C motif) receptor (CCR) 5 in neuropathic pain. METHODS: A spinal nerve injury model was established in adult male Wistar rats. The von Frey test and hot plate test were performed to evaluate neuropathic pain behavior, and real-time quantitative reverse transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry were performed to understand the molecular mechanisms. RESULTS: The expression levels of chemokine (C-C motif) ligand 3 and CCR5 messenger RNA in the spinal cord were up-regulated after nerve injury, which was possibly due to CD11b-positive microglia. Single intrathecal administration of recombinant chemokine (C-C motif) ligand 3 produced biphasic tactile allodynia; each phase of pain behavior was induced by different receptors. Intrathecal injection of CCR5 antagonist suppressed the development of tactile allodynia (12.81 ± 1.33 g vs. 3.52 ± 0.41 g [mean ± SEM, drug vs. control in paw-withdrawal threshold]; P < 0.05, n = 6 each) and could reverse established tactile allodynia (10.87 ± 0.91 g vs. 3.43 ± 0.28 g; P < 0.05, n = 8 and 7). Furthermore, Oral administration of CCR5 antagonist could reverse established tactile allodynia (8.20 ± 1.27 g vs. 3.18 ± 0.46 g; P < 0.05, n = 4 each). CONCLUSIONS: Pharmacological blockade of CCR5 was effective in the treatment of the development and maintenance phases of neuropathic pain. Thus, CCR5 antagonists may be potential new drugs for the treatment of neuropathic pain..
主要総説, 論評, 解説, 書評, 報告書等
主要学会発表等
学会活動
所属学会名
日本周産期麻酔科学会
日本老年麻酔学会
日本循環制御医学会
日本麻酔科学会
集中治療医学会
日本ペインクリニック学会
日本心臓血管麻酔学会
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2016年度      
受賞
最優秀演題賞, 日本麻酔科学会, 2012.05.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2020年度~2022年度, 若手研究, 代表, 周術期の急性腎障害の慢性腎臓病への移行に関する検討.

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