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Affiliation |
Graduate School of Medicine Doctorial Course in Medicine Bioregulatory Medicine Department of Biochemistry and Metabolic Science |
AN Jianbo
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Research Interests 【 display / non-display 】
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がん微小環境
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マクロファージ
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動脈硬化
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転移
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MRTF-A
Graduating School 【 display / non-display 】
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-2008.07
Peking University Faculty of Medicine Graduated
Graduate School 【 display / non-display 】
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-2013.09
Tokyo Medical and Dental University Doctor's Course Completed
Campus Career 【 display / non-display 】
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2019.04-Now
Akita University Graduate School of Medicine Doctorial Course in Medicine Bioregulatory Medicine Assistant Professor
Research Areas 【 display / non-display 】
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Life Science / Pathological biochemistry
Thesis for a degree 【 display / non-display 】
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IkBL is a new clue involved in the regulation of alternative splicing in human and viral genes
Jianbo An
2013.09 [Refereed]
Research Achievements 【 display / non-display 】
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Identification of Galectin-7 as a crucial metastatic enhancer of squamous cell carcinoma associated with immunosuppression.
Jianbo An, Yushi Nagaki, Satoru Motoyama, Yuta Kuze, Midori Hoshizaki, Kohei Kemuriyama, Tomokazu Yamaguchi, Takashi Ebihara, Yoshihiro Minamiya, Yutaka Suzuki, Yumiko Imai, Keiji Kuba
Oncogene 41 ( 50 ) 5319 - 5330 2022.12
Research paper (journal)
Metastasis predicts poor prognosis in cancer patients. It has been recognized that specific tumor microenvironment defines cancer cell metastasis, whereas the underlying mechanisms remain elusive. Here we show that Galectin-7 is a crucial mediator of metastasis associated with immunosuppression. In a syngeneic mouse squamous cell carcinoma (SCC) model of NR-S1M cells, we isolated metastasized NR-S1M cells from lymph nodes in tumor-bearing mice and established metastatic NR-S1M cells in in vitro culture. RNA-seq analysis revealed that interferon gene signature was markedly downregulated in metastatic NR-S1M cells compared with parental cells, and in vivo NR-S1M tumors heterogeneously developed focal immunosuppressive areas featured by deficiency of anti-tumor immune cells. Spatial transcriptome analysis (Visium) for the NR-S1M tumors revealed that various pro-metastatic genes were significantly upregulated in immunosuppressive areas when compared to immunocompetent areas. Notably, Galectin-7 was identified as a novel metastasis-driving factor. Galectin-7 expression was induced during tumorigenesis particularly in the microenvironment of immunosuppression, and extracellularly released at later stage of tumor progression. Deletion of Galectin-7 in NR-S1M cells significantly suppressed lymph node and lung metastasis without affecting primary tumor growth. Therefore, Galectin-7 is a crucial mediator of tumor metastasis of SCC, which is educated in the immune-suppressed tumor areas, and may be a potential target of cancer immunotherapy.
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ACE2-like enzyme B38-CAP suppresses abdominal sepsis and severe acute lung injury.
Takafumi Minato, Tomokazu Yamaguchi, Midori Hoshizaki, Satoru Nirasawa, Jianbo An, Saori Takahashi, Josef M Penninger, Yumiko Imai, Keiji Kuba
PloS one 17 ( 7 ) e0270920 2022.07
Research paper (journal)
Angiotensin-converting enzyme 2 (ACE2) is the carboxypeptidase to degrade angiotensin II (Ang II) to angiotensin 1-7 (Ang 1-7) and improves the pathologies of cardiovascular disease and acute respiratory distress syndrome (ARDS)/acute lung injury. B38-CAP is a bacteria-derived ACE2-like carboxypeptidase as potent as human ACE2 and ameliorates hypertension, heart failure and SARS-CoV-2-induced lung injury in mice. Recombinant B38-CAP is prepared with E. coli protein expression system more efficiently than recombinant soluble human ACE2. Here we show therapeutic effects of B38-CAP on abdominal sepsis- or acid aspiration-induced acute lung injury. ACE2 expression was downregulated in the lungs of mice with cecal ligation puncture (CLP)-induced sepsis or acid-induced lung injury thereby leading to upregulation of Ang II levels. Intraperitoneal injection of B38-CAP significantly decreased Ang II levels while upregulated angiotensin 1-7 levels. B38-CAP improved survival rate of the mice under sepsis. B38-CAP suppressed the pathologies of lung inflammation, improved lung dysfunction and downregulated elevated cytokine mRNA levels in the mice with acute lung injury. Thus, systemic treatment with an ACE2-like enzyme might be a potential therapeutic strategy for the patients with severe sepsis or ARDS.
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Peritumoral CD16b positive-neutrophil accumulation strongly correlates with regional lymph node metastasis in thoracic esophageal squamous cell cancer.
Hiromu Fujita, Satoru Motoyama, Jianbo An, Yushi Nagakai, Tomokazu Yamaguchi, Souichi Koyota, Yusuke Sato, Akiyuki Wakita, Kazuhiro Imai, Keiji Kuba, Yoshihiro Minamiya
Surgery 171 ( 6 ) 1535 - 1542 2022.06
Research paper (journal)
BACKGROUND: The mechanism underlying cancer cell metastasis from the tumor to regional lymph nodes is not yet fully understood. We hypothesized that peritumoral neutrophil accumulation promotes regional lymph node metastasis in thoracic esophageal squamous cell cancer. METHODS: Between 2010 and 2019, 126 thoracic esophageal squamous cell cancer patients received curative (R0) esophagectomy without preoperative treatment in our hospital. Using paraffin-embedded resected tumors, we performed immunohistochemical analysis of CD16b-positive neutrophil accumulation in the peritumoral area, which was defined as a 1-mm region centered on the border separating the malignant cell nests from the host tissue. The relationship between the density of peritumoral CD16b staining and pathological lymph node metastasis or 5-year overall survival was evaluated. RESULTS: Although the clinicopathological characteristics of CD16b-high and CD16b-low patients did not differ, greater pathological lymph node metastasis (P < .001) and lymphatic invasion by the tumor (P = .024) and a poorer 5-year survival (P = .010) were seen in CD16b-high patients. Moreover, CD16b-positive neutrophil density was generally higher in the peritumoral area than within the tumor itself. Univariate and multivariate analyses showed that CD16b-positive neutrophil accumulation was an independent factor for lymph node metastasis with an odds ratio >25 (P < .001). On the other hand, blood neutrophil counts did not correlate with lymph node metastasis. CONCLUSION: Peritumoral accumulation of CD16b-positive neutrophils is an independent factor strongly correlated with lymph node metastasis in thoracic esophageal squamous cell cancer.
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ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury.
Tomokazu Yamaguchi, Midori Hoshizaki, Takafumi Minato, Satoru Nirasawa, Masamitsu N Asaka, Mayumi Niiyama, Masaki Imai, Akihiko Uda, Jasper Fuk-Woo Chan, Saori Takahashi, Jianbo An, Akari Saku, Ryota Nukiwa, Daichi Utsumi, Maki Kiso, Atsuhiro Yasuhara, Vincent Kwok-Man Poon, Chris Chung-Sing Chan, Yuji Fujino, Satoru Motoyama, Satoshi Nagata, Josef M Penninger, Haruhiko Kamada, Kwok-Yung Yuen, Wataru Kamitani, Ken Maeda, Yoshihiro Kawaoka, Yasuhiro Yasutomi, Yumiko Imai, Keiji Kuba
Nature communications 12 ( 1 ) 6791 - 6791 2021.11
Research paper (journal)
Angiotensin-converting enzyme 2 (ACE2) is a receptor for cell entry of SARS-CoV-2, and recombinant soluble ACE2 protein inhibits SARS-CoV-2 infection as a decoy. ACE2 is a carboxypeptidase that degrades angiotensin II, thereby improving the pathologies of cardiovascular disease or acute lung injury. Here we show that B38-CAP, an ACE2-like enzyme, is protective against SARS-CoV-2-induced lung injury. Endogenous ACE2 expression is downregulated in the lungs of SARS-CoV-2-infected hamsters, leading to elevation of angiotensin II levels. Recombinant Spike also downregulates ACE2 expression and worsens the symptoms of acid-induced lung injury. B38-CAP does not neutralize cell entry of SARS-CoV-2. However, B38-CAP treatment improves the pathologies of Spike-augmented acid-induced lung injury. In SARS-CoV-2-infected hamsters or human ACE2 transgenic mice, B38-CAP significantly improves lung edema and pathologies of lung injury. These results provide the first in vivo evidence that increasing ACE2-like enzymatic activity is a potential therapeutic strategy to alleviate lung pathologies in COVID-19 patients.
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MRTF-A regulates proliferation and survival properties of pro-atherogenic macrophages.
Jianbo An, Taeko K Naruse, Kunihiko Hinohara, Yurie Soejima, Motoji Sawabe, Yasuaki Nakagawa, Koichiro Kuwahara, Akinori Kimura
Journal of molecular and cellular cardiology 133 26 - 35 2019.08
Research paper (journal)
We have previously reported that promoter polymorphism of myocardin-related transcription factor A (MRTF-A) is associated with coronary atherosclerosis. However, the contribution of MRTF-A to the development of atherosclerosis remains unknown. Macrophages are known to be important mediators of atherosclerosis. It has been demonstrated that local proliferation and survival of macrophages are atherogenic. In this study, we found that MRTF-A was highly expressed in lesional macrophages in human carotid atherosclerotic plaque. We then investigated the role of macrophagic MRTF-A in the pathogenesis of atherosclerosis. ApoE null MRTF-A transgenic mice (ApoE-/-/MRTF-Atg/+), in which human MRTF-A was specifically overexpressed in monocytes/macrophages, were established and fed with normal diet to examine the progression of atherosclerosis. We found that ApoE-/-/MRTF-Atg/+ aggravated atherosclerosis and lesional macrophages were more prominently accumulated in the aortic sinus of ApoE-/-/MRTF-Atg/+ than in that of ApoE-/- littermates. We also found that MRTF-A promoted proliferation and mitigated apoptosis of macrophages both in vitro and in vivo, and down regulated the expression of cyclin-dependent kinase inhibitors. From these findings, we conclude that MRTF-A modulates functional properties of pro-atherogenic macrophages. Our study may play a valuable role in understanding the pathological role of macrophagic MRTF-A in the progression of atherosclerosis.
◆Original paper【 display / non-display 】
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Grant-in-Aid for Scientific Research(C)
Project Year： 2022.04 - 2025.03
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The role of CCR4-NOT in the development of atherosclerosis
Grant-in-Aid for Early-Career Scientists
Project Year： 2020.04 - 2022.03 Investigator(s): An Jianbo
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The role of macrophagic MKL1 in the pathogenesis of atherosclerosis
Grant-in-Aid for Early-Career Scientists
Project Year： 2018.04 - 2020.03 Investigator(s): An Jianbo