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Article ; Online: New developments in the biology of fibroblast growth factors.

Ornitz, David M / Itoh, Nobuyuki

WIREs mechanisms of disease

2022 Volume 14, Issue 4, Page(s) e1549

Abstract: The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) ...

Abstract	The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltage-gated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases. This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology Congenital Diseases > Stem Cells and Development Cancer > Stem Cells and Development.
MeSH term(s)	Biology ; Fibroblast Growth Factors/genetics ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, Fibroblast Growth Factor/genetics ; Signal Transduction
Chemical Substances	Receptors, Fibroblast Growth Factor ; Fibroblast Growth Factors (62031-54-3) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2022-02-09
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2692-9368
ISSN (online)	2692-9368
DOI	10.1002/wsbm.1549
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Article ; Online: Task difficulty, risk feeling, and safety margin in the determination of driver behavior to prepare for traffic conflicts.

Kochi, Fuma / Saito, Yuichi / Uchida, Nobuyuki / Itoh, Makoto

Accident; analysis and prevention

2023 Volume 192, Page(s) 107284

Abstract: Unpredictable pedestrian and cyclist behavior associated with their appearance on the road in blind spots contributes to traffic near-misses or crashes. When experienced drivers are confronted with uncertainty, they take defensive measures called hazard- ... ...

Abstract	Unpredictable pedestrian and cyclist behavior associated with their appearance on the road in blind spots contributes to traffic near-misses or crashes. When experienced drivers are confronted with uncertainty, they take defensive measures called hazard-anticipatory driving, such as decreasing the vehicle velocity and/or increasing the lateral distance. Our research sought to understand the motivational determinants and perceptual processes that determine driver behavior in preparation for traffic conflicts with covert hazards. This study aimed to investigate the influence of driving experience on drivers' perceptions and behaviors to prepare for traffic conflicts. Two experiments were designed with 8 experienced and 13 inexperienced participants. In Experiment 1, participants were asked to provide their subjective impressions of task difficulty, feeling of risk, and statistical risk pertaining to assess their perceptions of the separation between task demand and capability after viewing animation clips of road scenes with blind intersections under different forced speeds. In Experiment 2, participants drove using a driving simulator in scenes with blind intersections, similar to those in Experiment 1. We sought to explore the motivational determinants of behavior regarding the relationship between subjective feelings and objective safety margins. The results showed that the driver's perception of task difficulty correlated with their driving speed, and inexperienced participants tended to underestimate task difficulty compared to experienced participants. The task difficulty and the feeling of risk were strongly correlated regardless of experience, and estimation of statistical risk differed depending on experience. The subjective task difficulty (and/or risk feeling) and objective safety margin were strongly correlated for experienced participants. Experienced participants who perceived a higher degree of difficulty in the forced-paced driving task tended to have greater safety margins in the self-paced driving task. These findings suggest that experienced participants with individually tolerable safety margins adjust their driving velocity and/or lateral distance in the control of task difficulty (and/or risk feeling) to prepare for traffic conflicts. Therefore, the underestimation of task difficulty should be considered when designing effective measures, such as driver assistance systems, to guide inexperienced drivers toward normative behaviors.
MeSH term(s)	Humans ; Accidents, Traffic/prevention & control ; Emotions ; Motivation ; Pedestrians ; Uncertainty
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Journal Article
ZDB-ID	210223-7
ISSN	1879-2057 ; 0001-4575
ISSN (online)	1879-2057
ISSN	0001-4575
DOI	10.1016/j.aap.2023.107284
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Zs.A 2461: Show issues

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Article ; Online: Reply to comments on "Ultrasonography in undergraduate medical education: a comprehensive review and the education program implemented at Jichi Medical University".

Kameda, Toru / Taniguchi, Nobuyuki / Konno, Kei / Koibuchi, Harumi / Omoto, Kiyoka / Itoh, Kouichi

Journal of medical ultrasonics (2001)

2023 Volume 50, Issue 4, Page(s) 587

MeSH term(s)	Humans ; Education, Medical, Undergraduate ; Universities ; Ultrasonography
Language	English
Publishing date	2023-08-07
Publishing country	Japan
Document type	Review ; Letter
ZDB-ID	1396630-3
ISSN	1613-2254 ; 0287-0592 ; 1346-4523
ISSN (online)	1613-2254
ISSN	0287-0592 ; 1346-4523
DOI	10.1007/s10396-023-01349-0
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Article ; Online: FGF10: A multifunctional mesenchymal-epithelial signaling growth factor in development, health, and disease.

Itoh, Nobuyuki

Cytokine & growth factor reviews

2016 Volume 28, Page(s) 63–69

Abstract: The FGF family comprises 22 members with diverse functions in development and health. FGF10 specifically activates FGFR2b in a paracrine manner with heparan sulfate as a co-factor. FGF10and FGFR2b are preferentially expressed in the mesenchyme and ... ...

Abstract	The FGF family comprises 22 members with diverse functions in development and health. FGF10 specifically activates FGFR2b in a paracrine manner with heparan sulfate as a co-factor. FGF10and FGFR2b are preferentially expressed in the mesenchyme and epithelium, respectively. FGF10 is a mesenchymal signaling molecule in the epithelium. FGF10 knockout mice die shortly after birth due to the complete absence of lungs as well as fore- and hindlimbs. FGF10 is also essential for the development of multiple organs. The phenotypes of Fgf10 knockout mice are very similar to those of FGFR2b knockout mice, indicating that FGF10 acts as a ligand that is specific to FGFR2b in mouse multi-organ development. FGF10 also plays roles in epithelial-mesenchymal transition, the repair of tissue injury, and embryonic stem cell differentiation. In humans, FGF10 loss-of-function mutations result in inherited diseases including aplasia of lacrimal and salivary gland, lacrimo-auriculo-dento-digital syndrome, and chronic obstructive pulmonary disease. FGF10 is also involved in the oncogenicity of pancreatic and breast cancers. Single nucleotide polymorphisms in FGF10 are also potential risk factors for limb deficiencies, cleft lip and palate, and extreme myopia. These findings indicate that FGF10 is a crucial paracrine signal from the mesenchyme to epithelium for development, health, and disease.
MeSH term(s)	Animals ; Cell Differentiation/physiology ; Epithelial-Mesenchymal Transition/physiology ; Fibroblast Growth Factor 10/metabolism ; Fibroblast Growth Factor 10/physiology ; Fibroblast Growth Factors/genetics ; Humans ; Mesoderm/cytology ; Mesoderm/metabolism ; Mice ; Mice, Knockout ; Paracrine Communication ; Receptor, Fibroblast Growth Factor, Type 2/genetics ; Receptor, Fibroblast Growth Factor, Type 2/immunology ; Receptor, Fibroblast Growth Factor, Type 2/metabolism ; Signal Transduction/physiology
Chemical Substances	FGF10 protein, human ; Fibroblast Growth Factor 10 ; Fibroblast Growth Factors (62031-54-3) ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.10.1)
Language	English
Publishing date	2016-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1330534-7
ISSN	1879-0305 ; 1359-6101
ISSN (online)	1879-0305
ISSN	1359-6101
DOI	10.1016/j.cytogfr.2015.10.001
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Article ; Online: A comparative study of natural variation in hemolymph glucose levels under different dietary sugar conditions in Drosophila melanogaster and D. simulans.

Inomata, Nobuyuki / Miyazaki, Manami / Noguchi, Mayu / Itoh, Masanobu

Genes & genetic systems

2022 Volume 97, Issue 5, Page(s) 221–227

Abstract: Physiological responses to environmental changes play important roles in adaptive evolution. In particular, homeostatic regulatory systems that maintain constant circulating glucose levels are crucial in animals. However, variation in circulating glucose ...

Abstract	Physiological responses to environmental changes play important roles in adaptive evolution. In particular, homeostatic regulatory systems that maintain constant circulating glucose levels are crucial in animals. However, variation in circulating glucose levels and the genetic effects on phenotypic variation in natural populations remain to be clarified. Here, we investigated the hemolymph glucose levels in natural populations of Drosophila melanogaster and its sibling species, D. simulans, in Japan. We quantified hemolymph glucose concentrations in third instar larvae of 27 lines for each species, which were reared on either glucose-free or glucose-rich food. In both species, genetic variation was not a major component of phenotypic variation on either glucose-free or glucose-rich food. The hemolymph glucose concentrations were much higher in D. simulans than in D. melanogaster. Genetic variance was larger in D. simulans than in D. melanogaster. The observed differences between the two species may be associated with the much more recent colonization history of D. simulans populations in Japan and/or the tolerance to environmental stresses. Our findings suggest that natural selection acting on hemolymph glucose levels in D. melanogaster is different from that in D. simulans.
MeSH term(s)	Animals ; Drosophila melanogaster/genetics ; Drosophila simulans/genetics ; Drosophila/genetics ; Hemolymph ; Selection, Genetic ; Species Specificity
Language	English
Publishing date	2022-12-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1323536-9
ISSN	1880-5779 ; 1341-7568
ISSN (online)	1880-5779
ISSN	1341-7568
DOI	10.1266/ggs.22-00059
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Zs.A 3466: Show issues

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Article: Unknown genes,

Miwa, Hiroyuki / Itoh, Nobuyuki

Heliyon

2018 Volume 4, Issue 9, Page(s) e00773

Abstract: We identified two genes, ...

Abstract	We identified two genes,
Language	English
Publishing date	2018-09-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2018.e00773
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Article ; Online: A secretory protein neudesin regulates splenic red pulp macrophages in erythrophagocytosis and iron recycling.

Nakayama, Yoshiaki / Masuda, Yuki / Mukae, Takehiro / Mikami, Tadahisa / Shimizu, Ryohei / Kondo, Naoto / Kitagawa, Hiroshi / Itoh, Nobuyuki / Konishi, Morichika

Communications biology

2024 Volume 7, Issue 1, Page(s) 129

Abstract: Neudesin, originally identified as a neurotrophic factor, has primarily been studied for its neural functions despite its widespread expression. Using 8-week-old neudesin knockout mice, we elucidated the role of neudesin in the spleen. The absence of ... ...

Abstract	Neudesin, originally identified as a neurotrophic factor, has primarily been studied for its neural functions despite its widespread expression. Using 8-week-old neudesin knockout mice, we elucidated the role of neudesin in the spleen. The absence of neudesin caused mild splenomegaly, shortened lifespan of circulating erythrocytes, and abnormal recovery from phenylhydrazine-induced acute anemia. Blood cross-transfusion and splenectomy experiments revealed that the shortened lifespan of erythrocytes was attributable to splenic impairment. Further analysis revealed increased erythrophagocytosis and decreased iron stores in the splenic red pulp, which was linked to the upregulation of Fcγ receptors and iron-recycling genes in neudesin-deficient macrophages. In vitro analysis confirmed that neudesin suppressed erythrophagocytosis and expression of Fcγ receptors through ERK1/2 activation in heme-stimulated macrophages. Finally, we observed that 24-week-old neudesin knockout mice exhibited severe symptoms of anemia. Collectively, our results suggest that neudesin regulates the function of red pulp macrophages and contributes to erythrocyte and iron homeostasis.
MeSH term(s)	Animals ; Mice ; Anemia ; Iron/metabolism ; Macrophages/metabolism ; Mice, Knockout ; Phagocytosis/physiology ; Receptors, IgG/metabolism ; Spleen/metabolism ; Intercellular Signaling Peptides and Proteins/metabolism ; Nerve Tissue Proteins/metabolism
Chemical Substances	Iron (E1UOL152H7) ; Receptors, IgG ; Intercellular Signaling Peptides and Proteins ; Nerve Tissue Proteins
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-024-05802-9
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Article: FGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases.

Itoh, Nobuyuki

Frontiers in endocrinology

2014 Volume 5, Page(s) 107

Abstract: Fibroblast growth factor (FGF) family members are mostly secreted as signaling proteins with diverse functions in development and metabolism. FGF21 is a unique FGF with metabolic, but not proliferative activities. FGF21 is mostly induced by different ... ...

Abstract	Fibroblast growth factor (FGF) family members are mostly secreted as signaling proteins with diverse functions in development and metabolism. FGF21 is a unique FGF with metabolic, but not proliferative activities. FGF21 is mostly induced by different kinds of stress and acts though FGF receptor 1c with β-Klotho as a cofactor in an endocrine or, in parts, autocrine/paracrine manner. Hepatic FGF21 directly acts on white adipocytes to inhibit lipolysis and acts through the brain to increase systemic glucocorticoid levels and suppress physical activity in response to starvation. It also protects against dioxin toxicity. Adipocytic FGF21 induces the browning of white adipose tissue (WAT) and activates brown adipocytes in response to cold exposure. It also acts as an upstream effector of adiponectin in white adipocytes. Myocytic FGF21 protects against diet-induced obesity and insulin resistance, induces the browning of WAT, and protects against cardiac hypertrophy. In addition, Fgf21 polymorphisms are possibly related with metabolic diseases and FGF21 are biomarker of metabolic diseases. These findings indicate that FGF21 plays roles as a hepatokine, adipokine, and myokine in metabolism, injury protection, and diseases.
Language	English
Publishing date	2014-07-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2014.00107
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Article ; Online: Three pediatric cases of symptomatic hyponatremia in Prader-Willi syndrome.

Oto, Yuji / Murakami, Nobuyuki / Nakagawa, Ryo / Itoh, Masatsune / Nagai, Toshiro / Matsubara, Tomoyo

Journal of pediatric endocrinology & metabolism : JPEM

2022 Volume 35, Issue 10, Page(s) 1302–1305

Abstract: Objectives: A recent large retrospective cohort study of cases of hyponatremia in Prader-Willi syndrome (PWS), conducted at nine reference centers, showed that severe hyponatremia was rare in PWS (0.5%); furthermore, all cases involved adults. Here, we ... ...

Abstract	Objectives: A recent large retrospective cohort study of cases of hyponatremia in Prader-Willi syndrome (PWS), conducted at nine reference centers, showed that severe hyponatremia was rare in PWS (0.5%); furthermore, all cases involved adults. Here, we describe three pediatric cases of severe hyponatremia in PWS, with neurological symptoms. Case presentation: The cases involved two girls and one boy, and only one patient showed uniparental disomy. All patients had hyponatremia during infancy and presented with clinical symptoms, such as convulsions. All three patients improved with intravenous fluids and fluid restriction, with no sequelae. Conclusions: We report three pediatric cases of symptomatic hyponatremia of unknown cause in PWS. In patients with PWS, especially those with neurological symptoms such as convulsions, it is necessary to take hyponatremia into consideration.
MeSH term(s)	Adult ; Child ; Female ; Humans ; Hyponatremia/complications ; Male ; Prader-Willi Syndrome/complications ; Retrospective Studies ; Seizures/complications ; Uniparental Disomy
Language	English
Publishing date	2022-07-12
Publishing country	Germany
Document type	Case Reports
ZDB-ID	1231070-0
ISSN	2191-0251 ; 0334-018X
ISSN (online)	2191-0251
ISSN	0334-018X
DOI	10.1515/jpem-2022-0127
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Article ; Online: Unknown genes, Cebelin and Cebelin-like, predominantly expressed in mouse brain

Hiroyuki Miwa / Nobuyuki Itoh

Heliyon, Vol 4, Iss 9, Pp e00773- (2018)

2018

Abstract: We identified two genes, Cebelin and Cebelin-like, encoding unknown proteins in mice. Cebelin and Cebelin-like consist of 168 and 167 amino acids with putative secreted signal sequences. However, Cebelin and Cebelin-like are cellular proteins not ... ...

Abstract	We identified two genes, Cebelin and Cebelin-like, encoding unknown proteins in mice. Cebelin and Cebelin-like consist of 168 and 167 amino acids with putative secreted signal sequences. However, Cebelin and Cebelin-like are cellular proteins not secreted proteins. Cebelin and Cebelin-like were predominantly expressed in the brain among major tissues examined. The expression of Cebelin in the brain was predominantly detected in the internal granule layer of the cerebellum.
Keywords	Developmental biology ; Biochemistry ; Molecular biology ; Neuroscience ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Language	English
Publishing date	2018-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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