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Article ; Online: Coupling of Cortical Hyperintense Signals and Increased Glucose Metabolism in a Case of Anti-GABA

Hashimoto, Kentaro / Nakamura, Takumi / Fujita, Yukio / Furuta, Minori / Makioka, Kouki / Shimoda, Yuki / Iizuka, Takahiro / Ikeda, Yoshio

Internal medicine (Tokyo, Japan)

2023 Volume 62, Issue 23, Page(s) 3545–3548

Abstract: We herein report a case of anti-gamma aminobutyric acid type A receptor antibody-associated encephalitis (anti- ... ...

Abstract	We herein report a case of anti-gamma aminobutyric acid type A receptor antibody-associated encephalitis (anti-GABA
MeSH term(s)	Humans ; Brain/pathology ; Receptors, GABA-A/metabolism ; Encephalitis/diagnostic imaging ; Encephalitis/drug therapy ; Magnetic Resonance Imaging/methods ; Antibodies ; Thymus Neoplasms/complications ; Methylprednisolone/therapeutic use ; Glucose/metabolism ; Autoantibodies
Chemical Substances	Receptors, GABA-A ; Antibodies ; Methylprednisolone (X4W7ZR7023) ; Glucose (IY9XDZ35W2) ; Autoantibodies
Language	English
Publishing date	2023-04-14
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.1535-22
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Article ; Online: Significance of Lipopolysaccharides in Gastric Cancer and Their Potential as a Biomarker for Nivolumab Sensitivity.

Nakazawa, Nobuhiro / Yokobori, Takehiko / Sohda, Makoto / Hosoi, Nobuhiro / Watanabe, Takayoshi / Shimoda, Yuki / Ide, Munenori / Sano, Akihiko / Sakai, Makoto / Erkhem-Ochir, Bilguun / Ogawa, Hiroomi / Shirabe, Ken / Saeki, Hiroshi

International journal of molecular sciences

2023 Volume 24, Issue 14

Abstract: Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer ... ...

Abstract	Lipopolysaccharides are a type of polysaccharide mainly present in the bacterial outer membrane of Gram-negative bacteria. Recent studies have revealed that lipopolysaccharides contribute to the immune response of the host by functioning as a cancer antigen. We retrospectively recruited 198 patients with gastric cancer who underwent surgery. The presence of lipopolysaccharides was determined using immunohistochemical staining, with the intensity score indicating positivity. The relationship between lipopolysaccharides and CD8, PD-L1, TGFBI (a representative downstream gene of TGF-β signaling), wnt3a, and E-cadherin (epithelial-mesenchymal transition marker) was also investigated. Thereafter, we identified 20 patients with advanced gastric cancer receiving nivolumab and investigated the relationship between lipopolysaccharides and nivolumab sensitivity. After staining for lipopolysaccharides in the nucleus of cancer cells, 150 negative (75.8%) and 48 positive cases (24.2%) were found. The lipopolysaccharide-positive group showed increased cancer stromal TGFBI expression (
MeSH term(s)	Humans ; Lipopolysaccharides ; Nivolumab/therapeutic use ; B7-H1 Antigen/genetics ; Stomach Neoplasms/drug therapy ; Retrospective Studies ; Biomarkers ; Cadherins/metabolism ; Transforming Growth Factor beta ; Epithelial-Mesenchymal Transition/genetics
Chemical Substances	Lipopolysaccharides ; Nivolumab (31YO63LBSN) ; B7-H1 Antigen ; Biomarkers ; Cadherins ; Transforming Growth Factor beta
Language	English
Publishing date	2023-07-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241411790
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Article ; Online: Infiltration of Gastric Cancer Stroma by Tumor-Infiltrating Lymphocytes Correlates with Mechanistic Target of Rapamycin Signaling.

Nakazawa, Nobuhiro / Sohda, Makoto / Katayama, Ayaka / Ide, Munenori / Shimoda, Yuki / Tateno, Kohei / Watanabe, Takayoshi / Sano, Akihiko / Sakai, Makoto / Yokobori, Takehiko / Ogawa, Hiroomi / Oyama, Tetsunari / Shirabe, Ken / Saeki, Hiroshi

Oncology

2023 Volume 101, Issue 8, Page(s) 520–526

Abstract: Introduction: We investigated whether the infiltration of tumor-infiltrating lymphocytes (TILs) in gastric cancer (GC), as evaluated by hematoxylin and eosin (H&E) staining, could be a prognostic marker. We also explored on the relationship between TILs ...

Abstract	Introduction: We investigated whether the infiltration of tumor-infiltrating lymphocytes (TILs) in gastric cancer (GC), as evaluated by hematoxylin and eosin (H&E) staining, could be a prognostic marker. We also explored on the relationship between TILs and mechanistic target of rapamycin (mTOR) and how it regulates immune effector responses in GC. Methods: A total of 183 patients with available data on TIL were included. TIL infiltration was evaluated using H&E staining. We also conducted immunohistochemistry to determine mTOR expression. Results: Positive TIL infiltration was defined as TILs ≥20%. There were 72 (39.3%) and 111 (60.7%) positive and negative cases, respectively. TILs positivity significantly correlated with both absence of lymph node metastasis (p = 0.037) and negative p-mTOR expression (p = 0.040). TIL infiltration correlated with a significantly better overall (p = 0.046) and disease-free (p = 0.020) survival. Conclusion: mTOR possibly suppresses TIL infiltration in GC. H&E staining is an effective tool for evaluating the immune status of GC patients. H&E staining may be used in clinical practice to monitor treatment response in GC.
MeSH term(s)	Humans ; Prognosis ; Lymphocytes, Tumor-Infiltrating/pathology ; Stomach Neoplasms ; Lymphatic Metastasis/pathology ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2023-06-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	250101-6
ISSN	1423-0232 ; 0030-2414
ISSN (online)	1423-0232
ISSN	0030-2414
DOI	10.1159/000531475
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Article ; Online: MAdCAM-1 targeting strategy can prevent colitic cancer carcinogenesis and progression via suppression of immune cell infiltration and inflammatory signals.

Ozawa, Naoya / Yokobori, Takehiko / Osone, Katsuya / Bilguun, Erkhem-Ochir / Okami, Haruka / Shimoda, Yuki / Shiraishi, Takuya / Okada, Takuhisa / Sano, Akihiko / Sakai, Makoto / Sohda, Makoto / Miyazaki, Tatsuya / Ide, Munenori / Ogawa, Hiroomi / Yao, Takashi / Oyama, Tetsunari / Shirabe, Ken / Saeki, Hiroshi

International journal of cancer

2023 Volume 154, Issue 2, Page(s) 359–371

Abstract: Chronic inflammation caused by infiltrating immune cells can promote colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) by activating inflammatory cytokine signalling through the IL-6/p-STAT3 and TNFα/NF-κB pathways. Mucosal addressin ...

Abstract	Chronic inflammation caused by infiltrating immune cells can promote colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) by activating inflammatory cytokine signalling through the IL-6/p-STAT3 and TNFα/NF-κB pathways. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on high endothelial venules promotes the migration of immune cells from the bloodstream to the gut via interaction with α4β7 integrin expressed on the immune cells. MAdCAM-1, has therefore drawn interest as a novel therapeutic target for treating active UC. However, the role of MAdCAM-1-positive endothelial cells in immune cell infiltration in dysplasia/colitic cancers remains unclear. We evaluated the expression of MAdCAM-1, CD31 and immune cell markers (CD8, CD68, CD163 and FOXP3) in samples surgically resected from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC), using immunohistochemical staining. We used an azoxymethane/dextran sodium sulphate mouse model (AOM/DSS mouse) to evaluate whether dysplasia/colitic cancer could be suppressed with an anti-MAdCAM-1 blocking antibody by preventing immune cell infiltration. The number of MAdCAM-1-positive vessels and infiltrating CD8
MeSH term(s)	Humans ; Animals ; Mice ; Colitis/chemically induced ; Colitis/metabolism ; NF-kappa B ; Endothelial Cells/metabolism ; Interleukin-6 ; Colitis, Ulcerative/complications ; Carcinogenesis ; Neoplasms/complications ; Inflammation/complications ; Dextran Sulfate
Chemical Substances	NF-kappa B ; Interleukin-6 ; Dextran Sulfate (9042-14-2)
Language	English
Publishing date	2023-09-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.34722
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: PROX1 Was Associated with LGR5 and Wnt Signaling and Contributed to Poor Prognosis in Gastric Cancer.

Nakazawa, Nobuhiro / Sohda, Makoto / Ide, Munenori / Shimoda, Yuki / Tateno, Kohei / Watanabe, Takayoshi / Sano, Akihiko / Sakai, Makoto / Yokobori, Takehiko / Ogawa, Hiroomi / Oyama, Tetsunari / Shirabe, Ken / Saeki, Hiroshi

Oncology

2022 Volume 100, Issue 11, Page(s) 569–575

Abstract: Introduction: We investigated whether the expression of prospero homeobox protein-1 (PROX1) in gastric cancer (GC) could be a prognostic marker. We also focused on the relationship between PROX1 and LGR5 and Wnt/β-catenin activity in GC.: Methods: A ... ...

Abstract	Introduction: We investigated whether the expression of prospero homeobox protein-1 (PROX1) in gastric cancer (GC) could be a prognostic marker. We also focused on the relationship between PROX1 and LGR5 and Wnt/β-catenin activity in GC. Methods: A total of 196 patients who underwent potentially curative surgery were collected and reviewed retrospectively. Immunohistochemistry was conducted and evaluated the expression PROX1, LGR5, Wnt3a, and β-catenin expression. And we evaluated the relationship between PROX1 expression and clinicopathological features. Results: The PROX1 low-expression group consisted of 105 patients (53.6%) and the high-expression group consisted of 91 patients (46.4%). For LGR5 expression, 76 patients (38.8%) were classified as low-expression, and 120 patients (61.2%) were classified as high-expression. The PROX1 low-expression group was significantly younger (p = 0.0095), had more intestinal type (p = 0.014), and had smaller tumor size (p = 0.013). The PROX1 high-expression group was significantly correlated with high LGR5 expression (p < 0.0001) and high Wnt3a expression (p = 0.012). In addition, there were significantly more cases of postoperative recurrence in the PROX1 high-expression group (p = 0.013). Conclusion: Our findings demonstrate that PROX1 correlated with the cancer stemness markers LGR5 and Wnt3a signaling in GC and had a poor prognosis including postoperative recurrence.
MeSH term(s)	Humans ; Stomach Neoplasms/pathology ; Wnt Signaling Pathway ; beta Catenin ; Retrospective Studies ; Prognosis ; Biomarkers, Tumor/metabolism ; Receptors, G-Protein-Coupled/metabolism
Chemical Substances	beta Catenin ; Biomarkers, Tumor ; LGR5 protein, human ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2022-09-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	250101-6
ISSN	1423-0232 ; 0030-2414
ISSN (online)	1423-0232
ISSN	0030-2414
DOI	10.1159/000526734
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Article ; Online: Fetal goiter identified in a pregnant woman with triiodothyronine-predominant graves' disease: a case report.

Fujishima, Akiko / Sato, Akira / Miura, Hiroshi / Shimoda, Yuki / Kameyama, Saeko / Ariake, Chika / Adachi, Hiroyuki / Fukuoka, Yuki / Terada, Yukihiro

BMC pregnancy and childbirth

2020 Volume 20, Issue 1, Page(s) 344

Abstract: Background: Approximately 10% of all Graves' disease cases are triiodothyronine (T3)-predominant. T3-predominance is characterized by higher T3 levels than thyroxine (T4) levels. Thyroid stimulating hormone receptor autoantibody (TRAb) levels are higher ...

Abstract	Background: Approximately 10% of all Graves' disease cases are triiodothyronine (T3)-predominant. T3-predominance is characterized by higher T3 levels than thyroxine (T4) levels. Thyroid stimulating hormone receptor autoantibody (TRAb) levels are higher in T3-predominant Graves' disease cases than in non-T3-predominant Graves' disease cases. Treatment with oral drugs is difficult. Here, we report a case of fetal goiter in a pregnant woman with T3-predominant Graves' disease. Case presentation: A 31-year-old woman had unstable thyroid function during the third trimester of pregnancy, making it impossible to reduce her dosage of antithyroid medication. She was admitted to our hospital at 34 weeks of gestation owing to hydramnios and signs of threatened premature labor, and fetal goiter (thyromegaly) was detected. The dose of her antithyroid medication was reduced, based on the assumption that it had migrated to the fetus. Subsequently, the fetal goiter decreased in size, and the hydramnios improved. The patient underwent elective cesarean delivery at 36 weeks and 5 days of gestation. The infant presented with temporary symptoms of hyperthyroidism that improved over time. Conclusions: The recommended perinatal management of Graves' disease is to adjust free T4 within a range from the upper limit of normal to a slightly elevated level in order to maintain the thyroid function of the fetus. However, in T3-predominant cases, free T4 levels may drop during the long-term course of the pregnancy owing to attempts to control the mother's symptoms of thyrotoxicosis. Little is known about the perinatal management and appropriate therapeutic strategy for T3-predominant cases and fetal goiter. Therefore, further investigation is necessary.
MeSH term(s)	Adult ; Antithyroid Agents/therapeutic use ; Female ; Goiter/congenital ; Goiter/diagnostic imaging ; Graves Disease/complications ; Graves Disease/drug therapy ; Humans ; Infant, Newborn ; Male ; Pregnancy ; Pregnancy Complications/diagnostic imaging ; Prenatal Care ; Thyroxine/therapeutic use ; Triiodothyronine ; Ultrasonography, Prenatal
Chemical Substances	Antithyroid Agents ; Triiodothyronine (06LU7C9H1V) ; Thyroxine (Q51BO43MG4)
Language	English
Publishing date	2020-06-03
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1471-2393
ISSN (online)	1471-2393
DOI	10.1186/s12884-020-03035-2
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Article ; Online: Comparison of Risk Factors for Locally Advanced Lower Rectal Cancer Recurrence Evaluated by Magnetic Resonance Imaging and Pathological Factors Analysed by Longitudinal Slicing Method.

Shiraishi, Takuya / Ogawa, Hiroomi / Kumasaka, Soma / Shimoda, Yuki / Osone, Katsuya / Okada, Takuhisa / Enokida, Yasuaki / Sano, Akihiko / Sakai, Makoto / Yokobori, Takehiko / Tsushima, Yoshito / Oyama, Tetsunari / Sohda, Makoto / Shirabe, Ken / Saeki, Hiroshi

Anticancer research

2021 Volume 41, Issue 6, Page(s) 3169–3178

Abstract: Background/aim: We compared the risk factors for locally advanced lower rectal cancer (LALRC) recurrence evaluated by preoperative magnetic resonance imaging (MRI) and pathological factors analysed via the longitudinal slicing method to identify high ... ...

Abstract	Background/aim: We compared the risk factors for locally advanced lower rectal cancer (LALRC) recurrence evaluated by preoperative magnetic resonance imaging (MRI) and pathological factors analysed via the longitudinal slicing method to identify high risk groups for recurrence. Patients and methods: This retrospective single-institution cohort study analysed 45 consecutive patients who underwent curative surgery for LALRC. Data were analysed by an experienced radiologist and pathologist. Results: Final preoperative extramural venous invasion (EMVI) and extramural depth of invasion (EMD) determined via MRI were significantly associated with EMVI and EMD determined via pathological analysis. The log-rank test for disease-free survival based on initial preoperative factors showed significantly poor prognoses for circumferential resection margin (CRM)-positive, EMVI-positive, and EMD-positive patients. Conclusion: Final preoperative EMVI and EMD determined via MRI correlated with pathological EMVI and EMD, especially in patients who did not undergo preoperative treatment. CRM, EMVI, and EMD determined via preoperative MRI were significant risk factors for recurrence.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Disease-Free Survival ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Rectal Neoplasms/diagnostic imaging ; Rectal Neoplasms/pathology ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2021-06-01
Publishing country	Greece
Document type	Comparative Study ; Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.15103
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Article ; Online: High L-Type Amino Acid Transporter 1 Levels Are Associated with Chemotherapeutic Resistance in Gastric Cancer Patients.

Nakazawa, Nobuhiro / Sohda, Makoto / Ide, Munenori / Shimoda, Yuki / Ubukata, Yasunari / Kuriyama, Kengo / Hara, Keigo / Sano, Akihiko / Sakai, Makoto / Yokobori, Takehiko / Ogawa, Hiroomi / Oyama, Tetsunari / Shirabe, Ken / Saeki, Hiroshi

Oncology

2021 Volume 99, Issue 11, Page(s) 732–739

Abstract: Introduction: We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy.: Methods: Immunohistochemistry ...

Abstract	Introduction: We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy. Methods: Immunohistochemistry was used to investigate LAT-1, CD98, and phosphorylated-mammalian target of rapamycin (p-mTOR) expression in 111 GC patients. To clarify whether LAT-1 influences the therapeutic effects of chemotherapy, the correlation between disease-free survival rates and LAT-1 was determined in 2 groups: 59 patients who did not undergo postoperative adjuvant chemotherapy and 52 patients who did undergo postoperative adjuvant chemotherapy. Results: LAT-1 was significantly correlated with CD98 and p-mTOR expressions. We did not find any statistically significant correlation between LAT-1 and recurrence in the nontreated group. In contrast, a significant association was found between LAT-1 expression and disease-free survival in the chemotherapy group. Moreover, multivariate regression analysis demonstrated that LAT-1 was an independent predictor of disease-free survival in the postoperative adjuvant chemotherapy group (p = 0.012). Conclusion: Our findings demonstrate that LAT-1 is a useful predictive marker for a successful postoperative adjuvant chemotherapy treatment.
MeSH term(s)	Aged ; Antimetabolites, Antineoplastic/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/metabolism ; Chemotherapy, Adjuvant/methods ; Disease-Free Survival ; Drug Combinations ; Drug Resistance, Neoplasm ; Female ; Fluorouracil/therapeutic use ; Fusion Regulatory Protein-1/metabolism ; Humans ; Immunohistochemistry/methods ; Large Neutral Amino Acid-Transporter 1/metabolism ; Male ; Middle Aged ; Neoplasm Recurrence, Local/metabolism ; Oxonic Acid/therapeutic use ; Phosphorylation ; Prognosis ; Prospective Studies ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/metabolism ; Stomach Neoplasms/surgery ; TOR Serine-Threonine Kinases/metabolism ; Tegafur/therapeutic use
Chemical Substances	Antimetabolites, Antineoplastic ; Biomarkers, Tumor ; Drug Combinations ; Fusion Regulatory Protein-1 ; Large Neutral Amino Acid-Transporter 1 ; SLC7A5 protein, human ; S 1 (combination) (150863-82-4) ; Tegafur (1548R74NSZ) ; Oxonic Acid (5VT6420TIG) ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2021-08-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	250101-6
ISSN	1423-0232 ; 0030-2414
ISSN (online)	1423-0232
ISSN	0030-2414
DOI	10.1159/000517371
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Article: Cytokines and Cytokine Receptors Involved in the Pathogenesis of Alzheimer's Disease.

Nagae, Tomone / Araki, Kiho / Shimoda, Yuki / Sue, Lucia I / Beach, Thomas G / Konishi, Yoshihiro

Journal of clinical & cellular immunology

2016 Volume 7, Issue 4

Abstract: Inflammatory mechanisms are implicated in the pathology of Alzheimer's disease (AD). However, it is unclear whether inflammatory alterations are a cause or consequence of neurodegeneration leading to dementia. Clarifying this issue would provide valuable ...

Abstract	Inflammatory mechanisms are implicated in the pathology of Alzheimer's disease (AD). However, it is unclear whether inflammatory alterations are a cause or consequence of neurodegeneration leading to dementia. Clarifying this issue would provide valuable insight into the early diagnosis and therapeutic management of AD. To address this, we compared the mRNA expression profiles of cytokines in the brains of AD patients with "non-demented individuals with AD pathology" and non-demented healthy control (ND) individuals. "Non-demented individuals with AD pathology" are referred to as high pathology control (HPC) individuals that are considered an intermediate subset between AD and ND. HPC represents a transition between normal aging and early stage of AD, and therefore, is useful for determining whether neuroinflammation is a cause or consequence of AD pathology. We observed that immunological conditions that produce cytokines in the HPC brain were more representative of ND than AD. To validate these result, we investigated the expression of inflammatory mediators at the protein level in postmortem brain tissues. We examined the protein expression of tumor necrosis factor (TNF)α and its receptors (TNFRs) in the brains of AD, HPC, and ND individuals. We found differences in soluble TNFα and TNFRs expression between AD and ND groups and between AD and HPC groups. Expression in the temporal cortex was lower in the AD brains than HPC and ND. Our findings indicate that alterations in immunological conditions involving TNFR-mediated signaling are not the primary events initiating AD pathology, such as amyloid plaques and tangle formation. These may be early events occurring along with synaptic and neuronal changes or later events caused by these changes. In this review, we emphasize that elucidating the temporal expression of TNFα signaling molecules during AD is important to understand the selective tuning of these pathways required to develop effective therapeutic strategies for AD.
Language	English
Publishing date	2016-08-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2684688-3
ISSN	2155-9899
ISSN	2155-9899
DOI	10.4172/2155-9899.1000441
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Article: Regulation of the KCNJ5 gene by SF-1 in the adrenal cortex: Complete genomic organization and promoter function

Nishikido, Ayaka / Okamura, Takashi / Nakajima, Yasuyo / Ishida, Emi / Miyamoto, Tomoko / Toki, Akiko-Katano / Matsumoto, Shunichi / Yoshino, Satoshi / Horiguchi, Kazuhiko / Saito, Tsugumichi / Yamada, Eijiro / Ozawa, Atsushi / Shimoda, Yuki / Oyama, Tetsunari / Yamada, Masanobu

Molecular and cellular endocrinology. 2020 Feb. 05, v. 501

2020

Abstract: Activating mutations in the KCNJ5 gene are responsible for the significant number of aldosterone-producing adenomas. To elucidate the molecular mechanisms underlying KCNJ5 expression, we characterized the entire human KCNJ5 gene. The gene spanned ... ...

Abstract	Activating mutations in the KCNJ5 gene are responsible for the significant number of aldosterone-producing adenomas. To elucidate the molecular mechanisms underlying KCNJ5 expression, we characterized the entire human KCNJ5 gene. The gene spanned approximately 29.8 kb and contained three exons and two introns. The strongest expression of KCNJ5 mRNA was observed in the adrenal gland. The promoter region contained a putative binding site for SF-1 at −1782 bp. A construct containing −2444 bp of the promoter region exhibited the strongest promoter activity in adrenal H295R cells, and the introduction of a mutation in the SF-1 binding site almost completely abolished promoter activity. Furthermore, deletion mutation, EMSA, and knockdown analyses revealed that SF-1 bound to this element and was functional. Immunochemistry showed that KCNJ5 was predominantly expressed in the zona glomerulosa, while SF-1 was ubiquitously expressed in the adrenal cortex. These results demonstrated that SF-1 mediates the expression of human KCNJ5 in the adrenal cortex.
Keywords	adrenal cortex ; binding sites ; exons ; humans ; immunochemistry ; introns ; messenger RNA ; promoter regions ; sequence deletion
Language	English
Dates of publication	2020-0205
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2019.110657
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