Hiroyasu Nakano

Publications (95) View all

• Source

  Available from: Takashi Nishina

  Dataset: 2012 Nishina Science Signaling

  Takashi Nishina, Sachiko Komazawa-Sakon, Saeko Yanaka, Xuehua Piao, Dong-Mei Zheng, Jiang-Hu Piao, Yuko Kojima, Shunhei Yamashina, Emiko Sano, Tracy Putoczki, Takahiro Doi, Takashi Ueno, Junji Ezaki, Hiroko Ushio, Matthias Ernst, Kouhei Tsumoto, Ko Okumura, Hiroyasu Nakano
• Source

  Available from: Hiroyasu Nakano

  Dataset: 2012 Piao Science Signaling Supple ra93

  Xuehua Piao, Sachiko Komazawa-Sakon, Takashi Nishina, Masato Koike, Jiang-Hu Piao, Hanno Ehlken, Hidetake Kurihara, Mutsuko Hara, Nico Van Rooijen, Günther Schütz, Masaki Ohmuraya, Yasuo Uchiyama, Hideo Yagita, Ko Okumura, You-Wen He, Hiroyasu Nakano
• Source

  Available from: Hiroyasu Nakano

  Dataset: 2010 Missiou Circ Res

  Emmanuel Charbonney, Pam Speight, András Masszi, Hiroyasu Nakano, András Kapus
• Article: Hyperosmotic stress regulates the distribution and stability of Myocardin-Related Transcription Factor, a key modulator of the cytoskeleton.

  Donald L Ly, Faiza Waheed, Monika Lodyga, Pam Speight, Andras Masszi, Hiroyasu Nakano, Maria Hersom, Stine F Pedersen, Katalin Szaszi, Andras Kapus
  [show abstract] [hide abstract]
  ABSTRACT: Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated co-activator of serum response factor is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid and transient translocation of MRTF from the cytosol to the nucleus in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF translocation, since siRNA-mediated GEF-H1 downregulation suppresses these responses. While the osmotically induced RhoA activation promotes nuclear MRTF accumulation, the concomitant activation of p38 MAP kinase mitigates this effect. Moderate hyperosmotic stress (600 mosM) drives MRTF-dependent transcription through the cis-element CArG box. Silencing or pharmacological inhibition of MRTF prevents the osmotic stimulation of CArG-dependent transcription, and renders the cells susceptible to osmotic shock-induced structural damage. Interestingly, strong hyperosmolarity promotes proteasomal degradation of MRTF, concomitant with apoptosis. Thus, MRTF is an osmosensitive and osmoprotective transcription factor, whose intracellular distribution is regulated by the GEF-H1/RhoA/ROK and p38 pathways. However, strong osmotic stress destabilizes MRTF, concomitant with apoptosis, implying that hyperosmotically induced cell death takes precedence over epithelial-myofibroblast transition, a potential consequence of MRTF-mediated phenotypic reprogramming.
  AJP Cell Physiology 10/2012; · 3.54 Impact Factor
• Source

  Available from: Hiroyasu Nakano

  Article: Aberrant accumulation of interleukin-10-secreting neutrophils in TRAF2-deficient mice.

  Jiang-Hu Piao, Hideo Yagita, Ko Okumura, Hiroyasu Nakano
  [show abstract] [hide abstract]
  ABSTRACT: Highly coordinated expression of inflammatory and anti-inflammatory cytokines is crucial for maintaining homeostasis of the gut that is constantly exposed to large amounts of commensal bacteria. We have previously reported that tumor necrosis factor (TNF) receptor-associated factor (Traf)2(-/-) mice spontaneously develop severe colitis and that the development of colitis largely depends on TNFα-dependent apoptosis of colonic epithelial cells. However, the detailed molecular mechanisms underlying the immunological disorders of Traf2(-/-) mice are not fully understood. Here we show that interleukin (IL)-10-secreting neutrophils accumulated in peripheral blood and bone marrow (BM) cells from Traf2(-/-) mice compared with those from wild-type mice. Treatment of Traf2(-/-) mice with neutralizing antibody against TNFα or crossing Traf2(-/-) mice with Tnfr1(-/-) mice reduced the percentages of IL-10-secreting neutrophils, suggesting that the development of IL-10-secreting neutrophils largely depended on TNFα signals. Moreover, stimulation of BM cells from wild-type mice with lipopolysaccharide and Pam3CS(K)4, a ligand for Toll-like receptor 4 and 2, respectively, induced differentiation of BM cells into IL-10-secreting neutrophils. These results suggest that the development of IL-10-secreting neutrophils is not restricted to Traf2(-/-) mice, but could be generalized to wild-type mice under certain conditions such as inflammation. Finally, combined treatment of Traf2(-/-) mice with neutralizing antibodies against TNFα and IL-10, but not each antibody alone, substantially ameliorated colitis and prolonged survival. Together, abrogation of immunosuppressive conditions mediated by IL-10-secreting neutrophils might be an alternative strategy to treat chronic inflammatory diseases at least under certain conditions.
  Immunology and Cell Biology 05/2012; 90(9):881-8. · 3.66 Impact Factor