Hiroki Hagiwara

Publications (9)26.81 Total impact

• Article: Histone deacetylase inhibitor trichostatin A enhances myogenesis by coordinating muscle regulatory factors and myogenic repressors.

  Hiroki Hagiwara, Fumiaki Saito, Toshihiro Masaki, Miki Ikeda, Ayami Nakamura-Ohkuma, Teruo Shimizu, Kiichiro Matsumura
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  ABSTRACT: Histone deacetylase inhibitors (HDACIs) are known to promote skeletal muscle formation. However, their mechanisms that include effects on the expression of major muscle components such as the dystrophin-associated proteins complex (DAPC) or myogenic regulatory factors (MRFs) remain unknown. In this study, we investigated the effects of HDACIs on skeletal muscle formation using the C2C12 cell culture system. C2C12 myoblasts were exposed to trichostatin A (TSA), one of the most potent HDACIs, and differentiation was subsequently induced. We found that TSA enhances the expression of myosin heavy chain without affecting DAPC expression. In addition, TSA increases the expression of the early MRFs, Myf5 and MEF2, whereas it suppresses the expression of the late MRF, myogenin. Interestingly, TSA also enhances the expression of Id1, Id2, and Id3 (Ids). Ids are myogenic repressors that inhibit myogenic differentiation. These findings suggest that TSA promotes gene expression in proliferation and suppresses it in the differentiation stage of muscle formation. Taken together, our data demonstrate that TSA enhances myogenesis by coordinating the expression of MRFs and myogenic repressors.
  Biochemical and Biophysical Research Communications 11/2011; 414(4):826-31. · 2.48 Impact Factor
• Article: Secretion of N-terminal domain of α-dystroglycan in cerebrospinal fluid.

  Fumiaki Saito, Yuko Saito-Arai, Ayami Nakamura-Okuma, Miki Ikeda, Hiroki Hagiwara, Toshihiro Masaki, Teruo Shimizu, Kiichiro Matsumura
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  ABSTRACT: α-Dystroglycan (α-DG) plays crucial roles in maintaining the stability of cells. We demonstrated previously that the N-terminal domain of α-DG (α-DG-N) is secreted by cultured cells into the culture medium. In the present study, to clarify its function in vivo, we generated a monoclonal antibody against α-DG-N and investigated the secretion of α-DG-N in human cerebrospinal fluid (CSF). Interestingly, we found that a considerable amount of α-DG-N was present in CSF. α-DG-N in CSF was a sialylated glycoprotein with both N- and O-linked glycan. These observations suggest that secreted α-DG-N may be transported via CSF and have yet unidentified effects on the nervous system.
  Biochemical and Biophysical Research Communications 07/2011; 411(2):365-9. · 2.48 Impact Factor
• Article: The sound field reproduction method based on the spacial covariances and its reproduction efficiency.

  Hiroki Hagiwara, Yoshinori Takahashi, Mikio Tohyama, Kazunori Miyoshi
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  ABSTRACT: This paper describes a sound field reproduction method based on the spatial covariances. Wave surface control and convoluting the head related transfer function are major techniques for sound field reproduction. On the contrary, Takahashi and Tohyama, coauthors of this report, considered that the spatial impressions of a sound field, which we perceive through our ears, are reproduced by preserving the relative relationship between the observation points even if the wave surface is not completely controlled. Moreover, they proposed a new sound field reproduction method that can control the point-to-point covariance in a sound field [19th ICA, RBA15-012]. In this work, we demonstrated about the differences between the covariance based method and the conventional methods, such as stereophonic playback and boundary surface control based on the Kirchhoff-Helmholtz equation. Then, we discussed the performances of several methods on the point of view of reproductivity and device cost.
  The Journal of the Acoustical Society of America 11/2008; 124(4):2455. · 1.55 Impact Factor
• Article: [Congenital muscular dystrophy and alpha-dystroglycanopathy].

  Fumiaki Saito, Kiichiro Matsumura, Hiroki Hagiwara, Teruo Shimizu
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  ABSTRACT: Congenital muscular dystrophy (CMD) refers to a heterogeneous group of muscular dystrophies with onset during the neonatal period. Among them, some types of CMD are characterized by the association of brain malformations and ocular abnormalities. Biochemical analyses revealed altered glycosylation and decreased laminin-binding activity of alpha-dystroglycan in these disorders, therefore they are correctively called alpha-dystroglycanopathy. Recently, mutations in the genes encoding demonstrated or putative glycosyltransferases have been identified in alpha-dystroglycanopathy. Fukuyama-type CMD and MDC1C are caused by mutations in the fukutin and fukutin-related protein (FKRP) genes, respectively. Mutations in the protein O-mannose beta-1, 2-N-acetylglucosaminyltransferase (POMGnT-1) and protein O-mannosyltransferase 1 and 2 (POMT1 and POMT2) genes cause muscle-eye-brain disease and Walker-Warburg syndrome, respectively. In addition, mutations in Large gene results in MDC1D. Furthermore, recent genotype-phenotype correlation analyses have revealed that the spectrum of phenotypes caused by mutations in these genes is much wider than originally assumed. In this review, we focus on the molecular pathomechanism and diverging clinical phenotypes of alpha-dystroglycanopathy.
  Rinsho shinkeigaku = Clinical neurology 09/2008; 48(8):543-9.
• Article: [A case of combined sensation disturbance and clumsiness of the left hand caused by an infarction localized to brodmann areas 1 and 2].

  Yumiko Kutoku, Hiroki Hagiwara, Yaeko Ichikawa, Katsuhiko Takeda, Yoshihide Sunada
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  ABSTRACT: A 70-year-old woman was admitted to our hospital with a complaint of numbness and clumsiness of the left hand. On physical examination 23 days after the onset of cerebral infarction, she showed no apparent muscle weakness. Although her elementary somatosensory function was mostly intact with a minimal joint position sensation disturbance, she showed disturbances in tactile recognition, two-point discrimination, and weight perception. She also had difficulty in discrete finger movement of her left hand, especially when her eyes were closed. Brain MRI disclosed a small infarction localized to Brodmann areas 1 and 2 in the right postcentral gyrus. In the left median nerve short-latency somatosensory evoked potentials (s-SEPs), the N20 potential was normally evoked. This finding also indicated that the area 3b was preserved. The sensory symptoms observed in this patient were compatible with the hierarchical somatosensory processing model in the postcentral gyrus proposed by Iwamura et al, in which the elementary sensation recognized in area 3 is transferred to areas 1 and 2, and then processed to discriminative sensation. The disturbed discrete finger movement in this patient probably resulted from impaired tactile recognition which could be compensated for by visual information.
  Rinsho shinkeigaku = Clinical neurology 05/2007; 47(4):151-5.
• Article: Muscular atrophy of caveolin-3-deficient mice is rescued by myostatin inhibition.

  Yutaka Ohsawa, Hiroki Hagiwara, Masashi Nakatani, Akihiro Yasue, Keiji Moriyama, Tatsufumi Murakami, Kunihiro Tsuchida, Sumihare Noji, Yoshihide Sunada
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  ABSTRACT: Caveolin-3, the muscle-specific isoform of caveolins, plays important roles in signal transduction. Dominant-negative mutations of the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy 1C (LGMD1C) with loss of caveolin-3. However, identification of the precise molecular mechanism leading to muscular atrophy in caveolin-3-deficient muscle has remained elusive. Myostatin, a member of the muscle-specific TGF-beta superfamily, negatively regulates skeletal muscle volume. Here we report that caveolin-3 inhibited myostatin signaling by suppressing activation of its type I receptor; this was followed by hypophosphorylation of an intracellular effector, Mad homolog 2 (Smad2), and decreased downstream transcriptional activity. Loss of caveolin-3 in P104L mutant caveolin-3 transgenic mice caused muscular atrophy with increase in phosphorylated Smad2 (p-Smad2) as well as p21 (also known as Cdkn1a), a myostatin target gene. Introduction of the myostatin prodomain, an inhibitor of myostatin, by genetic crossing or intraperitoneal administration of the soluble type II myostatin receptor, another inhibitor, ameliorated muscular atrophy of the mutant caveolin-3 transgenic mice with suppression of p-Smad2 and p21 levels. These findings suggest that caveolin-3 normally suppresses the myostatin-mediated signal, thereby preventing muscular atrophy, and that hyperactivation of myostatin signaling participates in the pathogenesis of muscular atrophy in a mouse model of LGMD1C. Myostatin inhibition may be a promising therapy for LGMD1C patients.
  Journal of Clinical Investigation 12/2006; 116(11):2924-34. · 15.39 Impact Factor
• Article: [Collier's sign in Miller Fisher syndrome].

  Masahiro Miyaishi, Shoji Hemmi, Hiroki Hagiwara, Tatsufumi Murakami, Yoshihide Sunada
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  ABSTRACT: Collier's sign is well known as unilateral or bilateral eyelid retraction due to midbrain lesions. This sign is usually caused by infarction, tumor, multiple sclerosis, neuro-degenerative disease, or encephalitis. We report a case of Miller Fisher syndrome (MFS) which demonstrated Collier's sign. A 54-year-old man developed ophthalmoplegia, ataxia, and areflexia two weeks after common cold-like symptoms. At the same time, bilateral upper eyelid retraction (Collier's sign) was remarkably observed. Serum anti-GQ1b antibody was positive. Albumino-cytologic dissociation was seen at two weeks after onset. We treated him with high dose intravenous immunogloblins (IVIg) for five days. There was remarkable improvement after the administration of IVIg, and there was a complete recovery from his eyelid retraction. All his symptoms of MFS also disappeared. The eyelid retraction of Collier's sign has been reported to occur with lesions in the rostral midbrain and posterior commissure. Therefore, Collier's sign in this patient suggested central nervous system involvement in the MFS. To our knowledge, this is the first report of MFS associated with Collier's sign.
  Rinsho shinkeigaku = Clinical neurology 11/2006; 46(10):712-4.
• Article: Bone marrow transplantation improves outcome in a mouse model of congenital muscular dystrophy.

  Hiroki Hagiwara, Yutaka Ohsawa, Shoji Asakura, Tatsufumi Murakami, Takanori Teshima, Yoshihide Sunada
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  ABSTRACT: We examined whether pathogenesis in dystrophin-deficient (mdx) mice and laminin-alpha2-deficient (dy) mice is ameliorated by bone marrow transplantation (BMT). Green fluorescent protein (GFP) mice were used as donors. In mdx mice, BMT failed to produce any significant differences in muscle pathology, although some GFP-positive fibers with restored dystrophin expression were observed. In contrast, in the dy mice, BMT led to a significant increase in lifespan and an increase in growth rate, muscle strength, and respiratory function. We conclude that BMT improved outcome in dy mice but not mdx mice.
  FEBS Letters 09/2006; 580(18):4463-8. · 3.54 Impact Factor
• Article: Mechanism of taxane neurotoxicity.

  Hiroki Hagiwara, Yoshihide Sunada
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  ABSTRACT: The two taxanes (paclitaxel and docetaxel) are widely employed in standard antineoplastic practice. Although these agents are now well established, some toxic side effects have been reported. Toxicity of these agents includes bone marrow suppression (principally neutropenia), hypersensitivity reactions, cutaneous reactions, edema and neurotoxicity. The most prominent neurotoxicity is a sensory neuropathy. Controlling neuropathy is crucial for maintaining the quality of life of patients because it is usually persistent and hard to manage. The precise mechanism for taxane-induced neuropathy is still unknown. The taxanes are known to promote aggregation of intracellular microtubules. Abnormal aggregation of microtubules in the neuronal cells may cause this neuropathy. In addition, the taxanes have been suggested to have intrinsic toxicity and directly injure the cells. A better understanding of the mechanism for this neuropathy may improve the quality of life of patients who undergo taxane antineoplastic therapy.
  Breast Cancer 02/2004; 11(1):82-5. · 1.36 Impact Factor