Department of Bioscience,
School of Science and Technology,
Kwansei Gakuin University


関西学院大学 理工学部 生命医化学専攻科
平井研究室




研究業績
原著論文 解説、総説  特許

Abe J,Aono Y,Hirai Y,(2024). The decline in cellular iron is crucial for differentiation in keratinocytes. Metallomics. 2024 Mar 6:mfae014.doi: 10.1093/mtomcs/mfae014. Online ahead of print.

Kobori M,Abe J,Saito R,Hirai Y.(2024). CAMSAP3,a microtubule orientation regulator plays a vital role in manifesting differentiation-dependent characteristics in keratinocytes. Exp Cell Res. 2024 Feb 1;435(1):113927.
doi: 10.1016/j.yexcr.2024.113927. Epub 2024 Jan 7.

Nozaki S.,Hirai Y. (2023). A crucial stem cell plasticity regulation pathway: identification of key elements using the NCCIT human embryonic carcinoma cell line.
J. Biochemistry doi: 10.1093/jb/mvad063 Online ahead of print

Matsuguchi S., Hirai Y. (2023). Syntaxin4,P-cadherin, and CCAAT enhancer binding protein β as signaling elements in the novel differentiation pathway for cultured embryonic stem cells. Biochem Biophys Res Commun. 14;672:27-35. doi: 10.1016/j.bbrc.2023.06.039. Online ahead of print.

Hayashi K., Nozaki S.,TokushimaK., Tanaka F.,Hirai Y.(2023). Role of syntaxin3 an apical polarity protein in poorly polarized keratinoytes: regulation of asymmetric barrier formations in the skin epidermis. Cell Tissue Res. https://doi.10.1007/s00441-023-03798-y. Online ahead of print.

Takeda Y*., Matsuguchi S*., Nozaki S., Mihara T., Abe J., Hirai Y. (2022). Suppression of P-cadherin expression as a key regulatory element for embryonic cell stemness. Cell Struc. Funct.48(1):49-57. In press. https://doi.org/10.1247/csf.22060

Hori H., Kotani A., Abe J., Matsuguchi S., Hirai Y. (2022). Extracellular epimorphin impairs expression and processing of profilaggrin in HaCaT keratinocytes. Cytotechnology 75(2):123-133. in press.https://doi.org/10.1007/s10616-022-00566-8

Hirose Y, Hirai Y(2021) Cooperation of membrane-translocated syntaxin4 and basement membrane for dynamic mammary epithelial morphogenesis. J Cell Sci.134(22):jcs258905. in press, https://doi.org/10.1242/jcs.258905.

・Yamada M, Hirai Y, Inoue D, Komatsu S, Uchida T, Kojima T, Tomiyasu T, Yoshikawa N, Oda T (2021) Increased expression of epimorphin in a peritoneal fibrosis mouse model. Perit Dial Int. in press, doi:10.1177/08968608211051572.

Tanaka F, Uda M, Hirose Y, Hirai Y. (2020) Restoration of calcium-induced differentiation potential and tight junction formation in HaCaT keratinocytes by functional attenuation of overexpressed high mobility group box-1 protein. Cytotechnology. 72(1):165−174. doi: 10.1007/s10616-019-00367-6.


・Adachi N
, Suzuki S, Matsuoka H, Fushimi S, Ono J, Ohta KI, Hirai Y, Miki T, Koshimizu H. (2018)  Corticotropin-releasing hormone-binding protein is up-regulated by brain-derived neurotrophic factor and is secreted in an activity-dependent manner in rat cerebral cortical neurons.  J Neurochem.  in press  doi: 10.1111/jnc.14310. https://www.ncbi.nlm.nih.gov/pubmed/29355947

・Hirose Y, Shirai K, Hirai Y.2018) Membrane-tethered syntaxin-4 locally abrogates E-cadherin function and activates Smad signals, contributing to asymmetric mammary epithelial morphogenesis. J Cell Biochem.  119:7525-7539 doi: 10.1002/jcb.27064. https://www.ncbi.nlm.nih.gov/pubmed/29767852

Kido T, Horigome T,
Uda M, Adachi N, Hirai Y.
(2017) Generation of iPS-derived model cells for analyses of hair shaft differantiation. Biotechniques .63:131-134 DOI 10.2144/0001/14589

Horigome T, Takumi S, Shirai K, Kido T, Hagiwara N, Nakashima A, Adachi N, Yano H, Hirai Y. (2017) Sulfated glycosaminoglycans and non-classically secreted proteins, basic FGF and epimorphin, coordinately regulate TGF-β-induced cell behaviors of human scar dermal fibroblasts. J. Dermatol Sci. 86:132-141 DOI 10.1016/j.jdermsci.2017.01.014

Hagiwara-Chatani N, Shirai K, Kido T, Horigome T,
Yasue A, Adachi N, Hirai Y. (2016) Membrane translocation of t-SNARE protein syntaxin-4 abrogates ground-state pluripotency in mouse enbryonic stem cells. Sci Rep.7:39863 DOI 10.1038/srep39868

Shirai K, Hagiwara N, Horigome T, Hirose Y, Kadono N, Hirai Y.
(2016) Extracellularly extruded syntaxin-4 binds to laminin and syndecan-1 to regulate mammary epithelial morphogenesis. J.Cell. Biochem 118:636-698 DOI 10.1002/jcb.25661

Masuda E, Shirai K, Maekubo K, Hirai Y. 2015 A newly established culture method highlights regulatory roles of retinoic acid on morphogenesis and calcification of mammalian limb cartilage. Biotechniques 58:318-324.

Kadono N, Hagiwara N, Tagawa T, Maekubo K, Hirai Y. (2015) Extracellularly extruded syntaxin4 is a potent cornification regulator of epidermal keratinocytes. Mol Med. 14:77-86

Miura Y., Hagiwara N.
, Radisky D.C., Hirai Y. 2014 CCAAT/enhancer binding protein beta (C/EBPβ) isoform balance as a regulator of epithelial-mesenchymal transition in mouse mammary epithelial cells. Exp Cell Res. 327:146-55

Fujimoto S, Takase T, Kadono N, Maekubo K, Hirai Y. (2014). Krtap11-1, a hair keratin-associated protein, as a possible crucial element for the physical properties of hair shafts. J. Dermatol Sci. 74(1):39-47

Okugawa Y., Hirai Y. (2013). A novel three-dimensional cell culture method to analyze epidermal cell differentiation in vitro. Methods Mol. Biol. [doi 10.1007/7651_2013_45] Springer

Miyazaki T., Kadono N., Konishi Y., Hagiwara N., Maekubo K., Hirai Y. (2013 Effluent syntaxin3 from dying cells affords protection against apoptosis in epidermal keratinocytes.Exp Dermatol.  22(12):845-847.

Hagiwara, N., Kadono,.N.,Miyazaki,T.,Maekubo, K., Hirai, Y. (2013). Extracellular syntaxin4 triggers the differentiation program in teratocarcinoma F9 cells with impacts on cell adhesion properties. Cell & Tissue Res 354(2):581-591

Bascom, J.L., Radisky, D.C., Koh, E., Fata, J.E., Lo, A., Mori, H., Roosta, N., Hirai, Y., Bissell, M.J. (2013). Epimorphin is a novel regulator of the progesterone receptor isoform-A. Cancer Res. Jul 18. 73:5719-5729

Shono, M., Yoshioka, R., Chatani, Y., Hirai, Y. (2013). Ectopic expression of syntaxin3 affects behaviors of B16 melanoma by controlling actin dynamics. Cell Struc. Funct.38(1):97-107

Okugawa, Y., Hirai, Y. (2013). Extracellular epimorphin modulates epidermal differentiation signals mediated by epidermal growth factor receptor. J Dermatol. Sci. 69, 236-242.

Takase T
, Hirai Y (2012). Identification of the C-terminal tail domain of AHF/Trichohyalin as the critical site for modulation of the keratin filamentous meshwork in the keratinocyte. J. Dermatol. Sci. 65;141-148 (DOI 10.1016/j.jdermsci.2011.12.014)

Kadono N, Miyazaki T, Okugawa Y, Nakajima K,Hirai Y (2012). The impact of extracellular syntaxin4 on HaCaT keratinocyte behavior. Biochem. Biophys. Res. Commun. 417;1200-1205 (DOI 10.1016 / j. bbrc. 2011. 12.107)

Aono Y, Hirai Y (2011). A culture system for the live analysis of successive developmental processes and the morphological control of mammalian vertebral cartilage. Cytotechnology 63,269-77.

Kinoshita N, Horie Y, Ohshima S, Hirai Y., Dohmen T, Jin M, Matsuhashi T, Sasaki J, Sasaki T, Iizuka M, Ohnishi H. (2011). Epimorphin protects hepatocytes from oxidative stress by inhibiting mitochondrial injury. J Gastroenterol Hepatol. 26:201-6.

Okugawa Y, Bascom J, and Hirai Y.(2010) Epimorphin-derived peptides remedy epidermal parakeratosis triggered by unsaturated fatty acid. J. Derm. Sci. 59:176-183

Yamada M, Oda T, Higashi K, Kushiyama T, Yamakami K, Hirai Y, Yamamoto K, Hyodo T, Suzuki S, Miura S,Kumagai H. (2010) Involvement of epimorphin in the repair of experimental renal fibrosis in mice. Lab Invest. 90:867-880.

Radisky DC, Stallings-Mann M, Hirai Y and Bissell MJ.(2009) Single proteins serve multiple functions in intracellular and extracellular environments Nat.Rev. Mol. Cell Biol. 10:228-234.

Chen CS, Nelson CM, Khauv D, Bennett S, Radisky ES, Hirai Y, Bissell MJ, Radisky DC.(2009) Homology with Vessicle Fusion Mediator Syntaxin-1a Predicts Determinants of Epimorphin/Syntaxin-2 Function in Mammary Epithelial Morphogenesis. J. Biol. Chem.
 284:6877-6884

Aono S., Hirai Y. (2008)  Phosphorylation of claudin-4 is required for tight junction formation in a human keratinocyte cell line. Exp. Cell Res. 2008 314:3326-3339

Yamamoto S., Hirai K., Hasegawa-Oka Y., Hirai Y. (2008) Molecular elements of the regulatory control of keratin filament modulator AHF/Trichohyalin in the hair follicle. Exp Dermatol. 18:152-159

Okugawa Y., Hirai Y. (2008) Overexpression of extracellular epimorphin leads to impaired epidermal differentiation in HaCaT keratinocytes. J. Invest. Dermatol. 128:1884-1893.

Miura K., Yoshino R.,, Hirai Y., Goto T., Ohshima S., Mikami K., Yoneyama K., Watanabe D., Sato M., Senoo H., Kodama Y., Osawa Y., Brenner D.A., Watanabe S. (2007) Epimorphin regulates spheroid formation by inducing proteases in rodent hepatocytes through NF-κB J. Hepatology. 47: 834-843.

Hirai Y., Bissell M.J., Radisky D.C. (2007) Extracellular localization of epimorphin/syntaxin-2. Blood. 110: 3082.

Hirai Y.,Nelson C.M., Yamazaki K., Takebe K., Przybylo J., Madden B., Radisky DC. (2007) Non-classical export of epimorphin and its adhesion to αv-integrin in regulation of epithelial morphogenesis. J Cell Sci. 120:2032-43.
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Iizuka M., Sasaki K., Hirai Y., Shindo K., Konno S., Itou H., Ohshima S., Horie Y., Watanabe S. (2007) Morphogenic protein epimorphin protects intestinal epithelial cells from oxidative stress by the activation of EGF receptor and MEK/ERK, PI3 kinase/Akt signals. Am J Physiol Gastrointest Liver Physiol. 292:G39-52.
関連のページはこちらから

Otani T., Ichii T., Aono S., Takeichi M. Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells.J Cell Biol. 2006 Oct 9;175(1):135-46. Epub 2006 Oct 2.

Yoshino R.., Miura K. ,Segawa D., Hirai Y., Goto T., Ohshima S., Mikami K.I.., Yoneyama K., Shibuya T., Watanabe D., Kataoka E., Takeuchi S., Endoh A., Sato W., Watanabe S. (2006) Epimorphin expression and stellate cell status in mouse liver injury.Hepatol Res. 34:238-249

Tulachan S.S., Doi R.., Hirai Y.,Kawaguchi Y., Koizumi M., Hembree M., Tei E., Crowley A., Yew H. ,McFall C., Prasadan K., Preuett B., Imamura M., and Gittes G.K. (2006) Mesenchymal epimorphin is important for pancreatic duct morphogenesis. Develop.Growth Differ. 48:65-72

Oka,Y., Sato Y., Tsuda H., Hanaoka K., Hirai Y.,and Takahashi Y., (2006) Epimorphin acts extracellularly to promote cell-sorting and aggregration during the condensation of vertebral cartilage. Dev.Biol. 291:25-37

Bascom J.L., FataJ.E., Hirai Y., Sternlicht M.D., and Bissell M.J. (2005) Epimorphin overexpression in the mouse-mammary gland promotes alveolar hyperplasia and mammary adenocarcinoma. Cancer Res. 65, 8617-8621

Hirai Y., Takebe K., and Nakajima K., (2005). Structural optimization of pep7, a small peptide extracted from epimorphin, for effective induction of hair follicle anagen. Exp. Dermatol 14,692-699

Qin J., Takahashi, Y., Isuzugawa, K., Imai, M., Yamamoto S., Hirai Y., and Imakawa K. (2005) Regulation of embryo outgrowth by a morphogenic factor, epimorphin, in the mouse. Mol Reproduction and Development. 70:455-63

Aono S., Legouis, R., Hoose, W.A., and Kemphues, K.J. (2004) PAR-3 is required for epithelial cell polarity in the distal spermatheca of C. elegans. Development 131, 2865-2874
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Andoh, A., Fujino, S., Hirai Y., and Fujiyama, Y. (2004) Epimorphin expression in human colonic myofibroblasts Int. J. Mol. Med. 13, 57-61

Takebe, K., Oka,Y., Radisky, D., Tsuda, H., Tochigui, K., Koshida, S., Kogo, K. and Hirai Y. (2003) Epimorphin acts to induce hair follicle anagen in C57BL/6 mice. FASEB J. 17, 2037-2047
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Radisky, D,Hirai Y., and Bissell, M.J. (2003) Delivering the message: epimorphin and mammary epithelial morphogenesis TRENDS Cell Biol. 13, 426-434

Shirasaka T., Iizuka M., Yukawa, M.,Hirai Y., Horie Y., Itou H., Kom-no S., Fukushima T. and Watanabe S. (2003) Altered expression of epimorphin in ulcerative colitis. J. Gastro. Hepatol. 18, 570-577

Simian, M., Hirai Y., Nerve, M., Werb, Z., Lochter, A. and Bissell, M.J. (2001). The interplay of matrix metalloproteinases, morphogen and growth factors is necessary for branching of mammary epithelial cells Development 128, 3117-3131

Hirai Y., Radisky, D., Boudreau, R., Simian, M., Stevens M.E., Oka,Y., Takebe K., Niwa S. and Bissell M.J. (2001). Epimorphin mediate mammary luminal morphogenesis through control of C/EBPb J. Cell Biol. 153, 785-794
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Lehnert, L., Lerch, MM., Hirai Y., Kruse M.L., Schmiegel W., and Kalthoff H. (2001). Autocrine stimulation of human pancreatic duct-like development by soluble isoform of epimorphin J. Cell Biol. 152, 911-921

Hirai Y. (2001) Epimorphin as a morphogen: does a protein for intracellular vesicular targeting act as an extracellular signaling molecule? Cell Biol. Int. 25, 193-195

Aono S.,Nakagawa S., Reynolds, A.B., and Takeichi M (1999) p120ctn acts as an inhibitory regulator of cadherin function in coloncarcinoma cells. J. Cell Biol. 145, 551-562
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Hirai Y., Lochter A., Galosy, S., Koshida, S., Niwa, S. and Bissell, M.J. (1998). Epimorphin functions as a key morphoregulator for mammary epithelial cells J. Cell Biol. 140, 159-169
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Koshida, S and Hirai Y. (1997). Identification of cellular recognition sequence of epimorphin and critical role of cell/epimorphin interaction in lung branching morphogenesis Biochem. Biophys. Res. Commun. 234,522-525

Oka,Y. and Hirai Y. (1996) Inductive influences of epimorphin on endothelial cells in vitro. Exp. Cell Res. 222, 189-198

Hirai Y. (1994) Sodium-dodecyl-sulfate-resistant complex formation of epimorphin monomers and
interaction of the 150KDa complex with the cell surface
 Eur.J. Biochem. 225, 1133-1139

Hirai Y., Nakagawa S., and Takeichi M., (1993) Reexamination of properties of epimorphin and its possible roles Cell 73, 426-427

Hirai Y. (1993) Molecular cloning of human epimorphin; Identification of isoforms and their unique properties Biochem. Biophys. Res. Commun. 191, 1332-1337

Hirai Y., Takebe, K., Takashina, M. Kobayashi, S. and Takeichi, M. (1992)  Epimorphin: A mesenchymal protein essential for epithelial morphogenesis Cell 69, 471-481

Hirai Y., Takebe, K., Nakajima, M. Takashina, M. and Iizuka, M. (1991) Extended expression of liver functions of hepatocytes in collagen-contained cell aggregates (cell packs) Cytotechnology 6, 209-217

Hirai Y., Nose, A., Kobayashi, S. and Takeichi, M. (1989) Exprtession and role of E- and P-cadherin adhesion molecules in embryonic histogenesis II. Skin morphogenesis Development 105, 271-277

Hirai Y., Nose, A., Kobayashi, S. and Takeichi, M. (1989) Exprtession and role of E- and P-cadherin adhesion molecules in embryonic histogenesis I. Lung epithelial morphogenesis Development 105, 263-270

Kitano H., Nakamura K., Hirai Y. Kaku T., Ise N. (1988 Restricted diffusion effect on the binding of proteins to porous polymer resins as studied by repetitive injection method. Biotechnology and Bioengineering 31:547-552.

Kitano H.,Hirai Y. Okada Y, Nakamura K., Ise N. (1987) Pulse injection analysis of the binding of serum proteins to porous polymer gels modified with formyl groups. J Chromatogr. 420:13-24.

Nakamura K.,Hirai Y. Kitano H., Ise N. (1987) Dynamic analysis of irreversible adsorption of protein on porous polymer resins as studied by pulse injection method. Biotechnology and Bioengineering 30:216-224.

Kitano H., Hirai Y., Nakamura K., Ise N. (1986) Assay of enzyme activities and low-molecular-mass constituents in serum using stopped-flow technique coupled with gel-permeation chromatography. J Chromatogr 383:229-231.

Nakamura K., Hirai Y., Kitano H. (1985) Binding of serum proteins to polymer gels. II. Binding mechanism to polyoxyphenol-formaldehyde gels. J Appl Biochem 7:145-154.