The investigation on the pathogenesis of fibrosis using scleroderma fibroblasts

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591350
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kumamoto University
• Principal Investigator: IHN Hironobu Kumamoto University, 生命科学研究部, 教授 (20282634)
• Project Period (FY): 2008 – 2010
• Keywords: collagen / TGF-β / extracellular matrix / signal transduction / transcriptional regulation

Research Abstract

We investigated scleroderma fibroblasts as an in vitro model of fibrosis. We have shown that scleroderma fibroblasts overexpressed thrombospondin-1 (TSP-1), one of extracellular matrix proteins, and down-regulated CD36, the ligand for TSP-1. These phenomenon were shown to be induced by autocrine transforming growth factor-β (TGF-β) signaling in scleroderma fibroblasts. Furthermore, forced overexpression of TSP-1 or knock-down of CD36 was shown to induce fibrosis.

Research Products

• [Journal Article] Circulating microRNA associated with TNF signaling pathway in patients with plaque psoriasis. (2011)
  • Author(s): Oyama R, Jinnin M, Kakimoto A, Kanemura H, Ichihara A, Fujisawa A, Honda N, Masuguchi S, Fukushima S, Maruo K, Ihn H.
  • Journal Title: J Dermatol Sci 61 Pages: 209-211
  • Peer Reviewed
• [Journal Article] Circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. (2011)
  • Author(s): Kanemura H, Fukushima S, Yamashita J, Honda N, Oyama R, Kakimoto A, Masuguchi S, Ishihara T, Inoue Y, Jinnin M, Ihn H.
  • Journal Title: J Dermatol Sci 61 Pages: 187-193
  • Peer Reviewed
• [Journal Article] Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-・ in normal dermal fibroblasts. (2011)
  • Author(s): Moriya C, Jinnin M, Yamane K, Maruo K, Muchemwa FC, Igata T, Makino T, Fukushima S, Ihn H.
  • Journal Title: J Invest Dermatol 131 Pages: 655-661
  • Peer Reviewed
• [Journal Article] Altered dynamics of TGF-・ receptors in scleroderma fibroblasts. (2011)
  • Author(s): Asano Y, Ihn H, Jinnin M, Tamaki K.
  • Journal Title: Ann Rheum Dis 70 Pages: 384-387
  • Peer Reviewed
• [Journal Article] Circulating miR-29a levels in patients with scleroderma spectrum disorder. (2011)
  • Author(s): Kawashita Y, Jinnin M, Makino T, Kajihara I, Makino K, Honda N, Masuguchi S, Fukushima S, Inoue Y, Ihn H.
  • Journal Title: J Dermatol Sci 61 Pages: 67-69
  • Peer Reviewed
• [Journal Article] Down-regulation of mir-424 contributes to the abnormal angiogenesis via MEK1 and cyclin E1 in senile hemangioma : its implications to therapy. (2010)
  • Author(s): Nakashima T, Jinnin M, Etoh T, Fukushima S, Masuguchi S, Maruo K, Inoue Y, Ishihara T, Ihn H.
  • Journal Title: PloS One 5 Pages: e14334
  • Peer Reviewed
• [Journal Article] Impaired lymphangiogenesis due to excess VEGF-D/Flt-4 signaling in the skin of patients with systemic sclerosis. (2010)
  • Author(s): Honda N, Jinnin M, Kajihara I, Makino T, Fukushima T, Ihn H.
  • Journal Title: Br J Dermatol 163 Pages: 776-780
  • Peer Reviewed
• [Journal Article] Serum TARC/CCL17 levels are increased in dermatomyositis associated with interstitial lung disease. (2010)
  • Author(s): Kawashima T, Tada Y, Asano Y, Yazawa N, Tomita M, Tamaki Z, Kubo M, Ihn H, Sugaya M, Kadono T, Tamaki K, Sato S.
  • Journal Title: J Dermatol Sci 60 Pages: 52-54
  • Peer Reviewed
• [Journal Article] Characterization of monocyte/macrophage subsets in the skin and peripheral blood derived from patients with systemic sclerosis. (2010)
  • Author(s): Higashi-Kuwata N, Jinnin M, Makino T, Fukushima S, Inoue Y, Muchemwa FC, Yonemura Y, Komohara Y, Takeya M, Mitsuya H, Ihn H.
  • Journal Title: Arhritis Res Ther 12 Pages: R128(1-10)
  • Peer Reviewed
• [Journal Article] Amelanotic malignant melanoma where primary lesion was discovered 5 years after metastasis in the lymph node. (2010)
  • Author(s): Kato T, Inoue Y, Ishihara T, Kageshita T, Ihn H.
  • Journal Title: J Dermatol 37 Pages: 730-734
  • Peer Reviewed
• [Journal Article] PDGFB quantification is a useful tool in the diagnosis of dermatofibrosarcoma protuberans : a study of 10 cases. (2010)
  • Author(s): Muchemwa FC, Wakasugi S, Honda Y, Ihn H.
  • Journal Title: Clin Exp Dermatol 35 Pages: 295-299
  • Peer Reviewed
• [Journal Article] A novel COL1A1 exon 14/PDGFB fusion gene in dermatofibrosarcoma protuberans (2010)
  • Author(s): Muchemwa FC, Jinnin M, Wakasugi S, Sakamoto M, Inoue Y, Ishihara T, Ihn H.
  • Journal Title: Eur J Dermatol 20 Pages: 390-391
  • Peer Reviewed
• [Journal Article] Serum levels of soluble vascular endothelial growth factor receptor-2 in patients with systemic sclerosis. (2010)
  • Author(s): Jinnin M, Makino T, Kajihara I, Honda N, Makino K, Ogata A, Ihn H.
  • Journal Title: Br J Dermatol 162 Pages: 751-758
  • Peer Reviewed
• [Journal Article] Basic fibroblast growth factor stimulates the proliferation of human dermal fibroblasts via the ERK1/2 and JNK pathways. (2010)
  • Author(s): Makino T, Jinnin M, Muchemwa F, Fukushima S, Ihn H.
  • Journal Title: Br J Dermatol 162 Pages: 717-723
  • Peer Reviewed
• [Journal Article] Supression of melanin production by expression of HSP70. (2010)
  • Author(s): Hoshino T, Matsuda M, Yamashita Y, Takehara M, Fukuya M, Mineda K, Maji D, Ihn H, Adachi H, Sobue G, Funasaka Y, Mizushima T.
  • Journal Title: J Biol Chem 285 Pages: 13254-13263
  • Peer Reviewed
• [Journal Article] Up-regulated type I collagen expression by the inhibition of Rac1 signaling pathway in human dermal fibroblasts. (2010)
  • Author(s): Igata T, Jinnin M, Makino T, Moriya C, Muchemwa F, Ishihara T, Ihn H.
  • Journal Title: Biochem Biophys Res Commun 393 Pages: 101-105
  • Peer Reviewed
• [Journal Article] Transglutaminase 1 preferred substrate prptide K5 is an efficient tool in diagnosis of lamellar ichthyosis. (2010)
  • Author(s): Akiyama M, Sakai K, Yanagi T, Fukushima S, Ihn H, Hitomi K, Shimizu H.
  • Journal Title: Am J Pathol 176 Pages: 1592-1599
  • Peer Reviewed
• [Journal Article] The expression of human high molecular weight melanoma-associated antigen in acral lentiginous melanoma. (2010)
  • Author(s): Nishi H, Inoue Y, Kageshita T, Takata M, Ihn H.
  • Journal Title: Bioscience Trends 4 Pages: 86-89
  • Peer Reviewed
• [Journal Article] Prevention of ultraviolet B radiation-induced epidermal damage by expression of heat shock protein 70. (2010)
  • Author(s): Matsuda M, Hoshino T, Yamashita Y, Tanaka KI, Maji D, Sato K, Adachi H, Sobue G, Ihn H, Funasaka Y, Mizushima T.
  • Journal Title: J Biol Chem 285 Pages: 5848-5858
  • Peer Reviewed
• [Journal Article] CD109 expression levels in human malignant melanoma. (2010)
  • Author(s): Ohshima Y, Yajima I, Yanagishita T, Kumasaka MY, Yanagishita T, Watanabe D, Takahashi M, Inoue Y, Ihn H, Matsumoto Y, Kato M.
  • Journal Title: J Dermatol Sci 57 Pages: 132-146
  • Peer Reviewed
• [Journal Article] Decreased serum IL-7 levels in patients with systemic sclerosis. (2009)
  • Author(s): Makino T, Johno T, Fukushima S, Wakasugi S, Inoue Y, Ihn H.
  • Journal Title: Clin Exp Rheumatol 54s Pages: 68-69
  • Peer Reviewed
• [Journal Article] Clinical usefulness of anti-RNA polymerase III antibody measurement by enzyme-linked immunosorbent assay. (2009)
  • Author(s): Satoh T, Ishikawa O, Ihn H, Endo H, Kawaguchi Y, Sasaki T, Goto D, Takahashi K, Takahashi H, Misaki Y, Mimori T, Muro Y, Yazawa N, Sato S, Takehara K, Kuwana M.
  • Journal Title: Rheumatology 48 Pages: 1570-1574
  • Peer Reviewed
• [Journal Article] Alternatively activated macrophages (M2 macrophages) in the skin of patients with localized scleroderma. (2009)
  • Author(s): Higashi-Kuwata N, Makino T, Inoue Y, Takeya M, Ihn H.
  • Journal Title: Exp Dermatol 18 Pages: 727-729
  • Peer Reviewed
• [Journal Article] The expression of SnoN in normal human skin and cutaneous keratinous neoplasms. (2009)
  • Author(s): Zhang X, Egawa K, Xie Y, Ihn H.
  • Journal Title: Int J Dermatol 48 Pages: 579-583
  • Peer Reviewed
• [Journal Article] Multiple antigen-targeted immunotherapy with α-galactosylceramide-loaded and genetically engineered dendritic cells derived from embryonic stem cells. (2009)
  • Author(s): Fukushima S, Hirata S, Motomura Y, Fukuma D, Matsunaga Y, Haruta M, Ikuta Y, Ikeda T, Kageshita T, Ihn H, Nishimura Y, Senju S.
  • Journal Title: J Immunotherapy 32 Pages: 219-231
  • Peer Reviewed
• [Journal Article] The prevalence of melanocytic nevi on the soles in the Japanese population. (2009)
  • Author(s): Kogushi-Nishi H, Kawasaki J, Kageshita T, Ishihara T, Ihn H.
  • Journal Title: J Am Acad Dermatol 60 Pages: 767-771
  • Peer Reviewed
• [Journal Article] Non-radioisotope method for diagnosing photosensitive disorders and a new marker for xeroderma pigmentosum variant. (2009)
  • Author(s): Hashimoto S, Egawa K, Ihn H, Tateishi S.
  • Journal Title: J Dermatol 36 Pages: 130-135
  • Peer Reviewed
• [Journal Article] Quick detection of herpes viruses from skin vesicles and exudates without nucleic acid extraction using the multiplex PCR method. (2008)
  • Author(s): Sakai K, Wakasugi S, Muchemwa FC, Ihn H.
  • Journal Title: Bioscience Trends 2 Pages: 164-168
  • Peer Reviewed
• [Journal Article] Adult-onset neurological degeneration in a patient with Cockayne syndrome and a null mutation in the CSB gene. (2008)
  • Author(s): Hashimoto S, Suga T, Kudo E, Ihn H, Uchino M, Tateishi S.
  • Journal Title: J Invest Dermatol 128 Pages: 1597-1599
  • Peer Reviewed
• [Journal Article] Immunohistochemical characterization of the cellular infiltrate in localized scleroderma. (2008)
  • Author(s): Xie Y, Zhang X, Wakasugi S, Makino T, Inoue Y, Ihn H.
  • Journal Title: Int J Dermatol 47 Pages: 438-442
  • Peer Reviewed
• [Journal Article] A new disorder in UV-induced skin cancer with defective DNA repair distinct from xeroderma pigmentosum or Cocyayne syndrome. (2008)
  • Author(s): Hashimoto S, Egawa K, Ihn H, Igarashi A, Matsunaga T, Tateishi S, Yamaizumi M.
  • Journal Title: J Invest Dermatol 128 Pages: 694-701
  • Peer Reviewed
• [Journal Article] Autocrine TGF-β signaling in the pathogenesis of systemic sclerosis. (2008)
  • Author(s): Ihn H.
  • Journal Title: J Dermatol Sci 49 Pages: 103-113
  • Peer Reviewed
• [Journal Article] The expression levels of thrombospondin-1 in dermatofibroma and dermatofibrosarcoma protuberans.
  • Author(s): Maekawa T, Jinnin M, Ihn H.
  • Journal Title: Eur J Dermatol in press.
• [Journal Article] Analysis of adiponectin expression in rheumatic diseases.
  • Author(s): Arakawa H, Jinnin M, Muchemwa FC, Makino T, Kajihara I, Makino K, Honda N, Sakai K, Fukushima S, Ihn H.
  • Journal Title: Exp Dermatol in press.
• [Journal Article] Immunohistochemical characterization of the cellular infiltrate in discoid lupus erythematosus.
  • Author(s): Xie Y, Jinnin M, Zhang X, Wakasugi S, Makino T, Inoue Y, Masuguchi S, Sakai K, Jinnin M, Ihn H.
  • Journal Title: BioScience Trends in press.
• [Journal Article] Clinical significance of cobble stone appearance on the skin of patients with systemic sclerosis.
  • Author(s): Kajihara I, Jinnin M, Makino T, Toihata-Yonemitsu A, Fukushima S, Ihn H.
  • Journal Title: J Eur Acad Dermatol Venereol in press.
• [Journal Article] Expression pattern of new vessels arise related factors, VEGF1,2,3, and D2-40 protein, in the skin of patients with systemic sclerosis.
  • Author(s): Kuwata N, Makino T, Inoue Y, Ihn H.
  • Journal Title: Eur J Dermatol in press.
• [Journal Article] Serum levels of soluble CD163 in patients with systemic sclerosis.
  • Author(s): Nakayama W, Jinnin M, Makino K, Kajihara I, Makino T, Fukushima S, Inoue Y, Ihn H.
  • Journal Title: Rheumatol Int in press.
• [Journal Article] Serum levels of soluble CD21 in patients with sclerosis.
  • Author(s): Tomita M, Kadono T, Yazawa N, Kawashima T, Tamaki Z, Ashida R, Ohmatsu H, Asano Y, Sugaya M, Kubo M, Ihn H, Tamaki K, Sato S.
  • Journal Title: Rheumatol Int in press
• [Presentation] 全身性強皮症の病因について (2010)
  • Author(s): 尹浩信
  • Organizer: 第54回日本リウマチ学会総会・学術集会
  • Place of Presentation: 神戸ポートピアホテル・神戸
  • Year and Date: 20100422-20100425
• [Presentation] Molecular mechanism of fibrosis. (Invited Lecture) (2010)
  • Author(s): 尹浩信
  • Organizer: The 21th Academic Meeting of Korean Society for Investigative Dermatology
  • Place of Presentation: Auditorium, 1st Floor, Clinical Research Institute Seoul National University Hospital, Seoul, Korea
  • Year and Date: 20100402-20100403
• [Book] 強皮症2009(リウマチ病セミナーXXI) (2011)
  • Author(s): 尹浩信
  • Total Pages: 30-33
  • Publisher: 永井書店
• [Book] 全身性強皮症(皮膚疾患最新の治療2009-2010) (2009)
  • Author(s): 尹浩信
  • Total Pages: 78-79
  • Publisher: 南江堂