the role of long non-coding RNAs in the pathogenesis of sclerodermic skin diseases

• Project/Area Number: 15K09771
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Wakayama Medical University (2017); Kumamoto University (2015-2016)
• Principal Investigator: Jinnin Masatoshi 和歌山県立医科大学, 医学部, 教授 (60401048)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 膠原病 / 全身性強皮症 / RNＡ / rna / ｒｎａ

Outline of Final Research Achievements

We tried to evaluate the expression of long non-coding RNAs (lncRNAs) in scleroderma patients and determined whether lncRNAs controls collagen expression in dermal fibroblasts. lncRNA expression was examined by real-time PCR and in situ hybridization. We found one of the lncRNAs, TSIX, was overexpressed in scleroderma dermal fibroblasts both in vivo and in vitro. TSIX siRNA decreased the mRNA expression of type I collagen in normal and sclerderma dermal fibroblasts. Furthermore, TSIX siRNA significantly reduced type I collagen mRNA stability, but not protein half-lives. We first showed that serum TSIX levels were significantly increased in scleroderma patients. TSIX siRNA also attenuated the dermal thickening induced by bleomycin injection.
Our study demonstrated that TSIX plays a role in the pathogenesis of scleroderma, and may become a key molecule to develop novel diagnostic tool or therapeutic approach.

Research Products

• [Journal Article] Regulatory mechanisms of collagen expression by interleukin-22 signaling in scleroderma fibroblasts. (2018)
  • Author(s): Sawamura S, Jinnin M, Inoue K, Yamane K, Honda N, Kajihara I, Makino T, Masuguchi S, Fukushima S, Ihn H.
  • Journal Title: J Dermatol Sci. Volume: 90 Pages: 52-59
  • Peer Reviewed
• [Journal Article] The role of miR-210, E2F3 and ephrin A3 in angiosarcoma cell proliferation. (2017)
  • Author(s): Nakashima S, Jinnin M, Kanemaru H, Kajihara I, Igata T, Okamoto S, Tazaki Y, Harada M, Masuguchi S, Fukushima S, Masuzawa M, Amoh Y, Masuzawa M, Ihn H.
  • Journal Title: Eur J Dermatol. Volume: 27 Issue: 5 Pages: 464-471
  • DOI: 10.1684/ejd.2017.3084
  • Peer Reviewed
• [Journal Article] Serum levels of genomic DNA of α1(I) collagen are elevated in scleroderma patients. (2017)
  • Author(s): Sawamura S, Jinnin M, Shimbara M, Nakamura K, Kudo H, Inoue K, Nakayama W, Kajihara I, Fukushima S, Ihn H.
  • Journal Title: J Dermatol. Volume: 印刷中 Issue: 8 Pages: 927-931
  • DOI: 10.1111/1346-8138.13838
  • Peer Reviewed
• [Journal Article] Long non-coding RNA TSIX is upregulated in scleroderma dermal fibroblasts and controls collagen mRNA stabilization. (2016)
  • Author(s): Wang Z, Jinnin M, Nakamura K, Harada M, Kudo H, Nakayama W, Inoue K, Nakashima T, Honda N, Fukushima S, Ihn H.
  • Journal Title: Exp Dermatol. Volume: 25 Issue: 2 Pages: 131-136
  • DOI: 10.1111/exd.12900
  • Peer Reviewed
• [Journal Article] Establishment and gene expression analysis of disease-derived induced pluripotent stem cells of scleroderma. (2016)
  • Author(s): Wang Z, Nakamura K, Jinnin M, Kudo H, Goto M, Era T, Kira T, Nakashima T, Fukushima S, Ihn H.
  • Journal Title: J Dermatol Sci Volume: 84 Issue: 2 Pages: 186-196
  • DOI: 10.1016/j.jdermsci.2016.08.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dysregulated interleukin-23 signalling contributes to the increased collagen production in scleroderma fibroblasts via balancing microRNA expression. (2016)
  • Author(s): Nakayama W, Jinnin M, Tomizawa Y, Nakamura K, Kudo H, Inoue K, Makino K, Honda N, Kajihara I, Fukushima S, Ihn H.
  • Journal Title: Rheumatology (Oxford) Volume: 56 Issue: 1 Pages: 145-155
  • DOI: 10.1093/rheumatology/kew336
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Serum long non-coding RNA, snoRNA host gene 5 level as a new tumor marker of malignant melanoma. (2015)
  • Author(s): Ichigozaki Y, Fukushima S, Jinnin M, Miyashita A, Nakahara S, Tokuzumi A, Yamashita J, Kajihara I, Aoi J, Masuguchi S, Zhongzhi W, Ihn H.
  • Journal Title: Exp Dermatol. Volume: 25 Issue: 1 Pages: 67-69
  • DOI: 10.1111/exd.12868
  • Peer Reviewed / Open Access
• [Presentation] Longitudinal changes in dermoscopic findings of infantile hemangioma. (2016)
  • Author(s): Jinnin M
  • Organizer: International Master Course on Aging Science
  • Place of Presentation: Taipei
  • Int'l Joint Research