The role of microRNA let-7a in systemic sclerosis

• Project/Area Number: 25870555
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology; Collagenous pathology/Allergology
• Research Institution: Kumamoto University
• Principal Investigator: MAKINO Katsunari 熊本大学, 医学部附属病院, 非常勤診療医師 (00433037)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 全身性強皮症 / マイクロRNA / let-7a / 皮膚線維芽細胞 / コラーゲン / microRNA / 限局性強皮症 / 血清microRNA / extracellular matrix

Outline of Final Research Achievements

In this project, we demonstrated the role of microRNA let-7a against skin fibrosis in systemic sclerosis (SSc). The let-7a was the potent regulator of type I collagen. The let-7a levels in dermal fibroblasts and sera of SSc patients were lower than those in healthy control. This down-regulation of let-7a in SSc led to the overexpression of type I collagen. We confirmed that the improvement of bleomycin-induced dermal thickening by let-7a administration. Investigation of more detailed mechanisms of miRNA-mediated regulation of collagen expression may lead to new therapeutic approach against systemic sclerosis.

Research Products

• [Journal Article] Serum levels of soluble carbonic anhydrase IX are decreased in patients with diffuse cutaneous systemic sclerosis compared to those with limited cutaneous systemic sclerosis (2014)
  • Author(s): Makino K, Jinnin M, Makino T, Kajihara I, Fukushima S, Inoue Y, Ihn H
  • Journal Title: Biosci Trends. Volume: 8 Pages: 144-148
  • NAID: 130004572597
  • Peer Reviewed
• [Journal Article] Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing (2014)
  • Author(s): Makino K, Jinnin M, Aoi J, Kajihara I, Makino T, Fukushima S, Sakai K, Nakayama K, Emoto N, Yanagisawa M, Ihn H
  • Journal Title: PLoS One. Volume: 22
  • Peer Reviewed
• [Journal Article] Down-regulation of microRNA-196a in the sera and involved skin of localized scleroderma patients (2014)
  • Author(s): Takamitsu Makino; Masatoshi Jinnin; Mitsuhiko Etoh; Keitaro Yamane; Ikko Kajihara; Katsunari Makino; Asako Ichihara; Toshikatsu Igata; Keisuke Sakai; Satoshi Fukushima;
  • Journal Title: European Journal of Dermatology Volume: 24(4) Issue: 4 Pages: 760-6
  • DOI: 10.1684/ejd.2014.2384
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The expression profile of the toll-like receptor family in scleroderma dermal fibroblasts (2014)
  • Author(s): Sakoguchi A, Nakayama W, Jinnin M, Wang Z, Yamane K, Aoi J, Makino K, Kajihara I, Ichihara A, Makino T, Fukushima S, Sakai K, Inoue Y, Ihn H
  • Journal Title: Clin Exp Rheumatol. Volume: 32
  • Peer Reviewed
• [Journal Article] Immunoglobulin G4-related disease in a psoriasis vulgaris patient treated with ustekinumab. (2014)
  • Author(s): Kajihara I, Makino K, Ichihara A, Fukushima S, Jinnin M, Hirooka S, Kojima K, Kourogi H, Ihn H.
  • Journal Title: J Dermatol. Volume: 41 Issue: 7 Pages: 670-1
  • DOI: 10.1111/1346-8138.12528
  • Peer Reviewed
• [Journal Article] Increased CCL22 expression in psoriatic skin predicts a good response to infliximab therapy. (2014)
  • Author(s): Kusumoto S, Kajihara I, Nagamoto E, Makino K, Ichihara A, Aoi J, Johno T, Makino T, Fukushima S, Jinnin M, Ihn H.
  • Journal Title: Br J Dermatol. Volume: 171 Issue: 5 Pages: 1259-61
  • DOI: 10.1111/bjd.13091
  • Peer Reviewed
• [Journal Article] MIRSNP rs2910164 of miR-146a is associated with the muscle involvement in polymyositis/dermatomyositis. (2014)
  • Author(s): Okada Y, Jinnin M, Makino T, Kajihara I, Makino K, Honda N, Nakayama W, Inoue K, Fukushima S, Ihn H
  • Journal Title: Int J Dermatol Volume: 53 Pages: 300-304
  • Peer Reviewed
• [Journal Article] A case of psoriasis accompanied by arthritis after delivery (2014)
  • Author(s): Kanemaru H, Jinnin M, Asao K, Ichihara A, Makino K, Kajihara I, Fujisawa A, Fukushima S, Ihn H.
  • Journal Title: Biosci Trends Volume: 8 Pages: 64-67
  • NAID: 130003397286
  • Peer Reviewed
• [Journal Article] Detection of hair root miR-19a as a novel diagnostic marker for psoriasis (2013)
  • Author(s): Hirao H, Jinnin M, Ichihara A, Fujisawa A, Makino K, Kajihara I, Sakai K, Fukushima S, Inoue Y, Ihn H
  • Journal Title: Eur J Dermatol Volume: 23 Pages: 807-811
  • Peer Reviewed
• [Journal Article] Detection of hair-microRNAs as the novel potent biomarker: Evaluation of the usefulness for the diagnosis of scleroderma. (2013)
  • Author(s): Wang Z, Jinnin M, Kudo H, Inoue K, Nakayama W, Honda N, Makino K, Kajihara I, Fukushima S, Inoue Y, Ihn H.
  • Journal Title: J Dermatol Sci Volume: 72 Issue: 2 Pages: 134-41
  • DOI: 10.1016/j.jdermsci.2013.06.018
  • Peer Reviewed
• [Journal Article] Serum levels of tenascin-C in collagen diseases. (2013)
  • Author(s): Inoue K, Jinnin M, Hara Y, Makino K, Kajihara I, Makino T, Sakai K, Fukushima S, Inoue Y, Ihn H.
  • Journal Title: J DermatoL Volume: 40 Issue: 9 Pages: 715-9
  • DOI: 10.1111/1346-8138.12218
  • Peer Reviewed
• [Journal Article] Expression analysis of multiple microRNAs in each patient with scleroderma. (2013)
  • Author(s): Koba S, Jinnin M, Inoue K, Nakayama W, Honda N, Makino K, Kajihara I, Makino T, Fukushima S, Ihn H.
  • Journal Title: Experimental Dermatology Volume: 22 Issue: 7 Pages: 489-491
  • DOI: 10.1111/exd.12173
  • Peer Reviewed
• [Journal Article] Case of neuro-Behçet's disease successfully maintained a remission using infliximab for 2 years (2013)
  • Author(s): Kanemaru H, Makino T, Jinnin M, Yonemitsu A, Makino K, Ihn H
  • Journal Title: J Dermatol Volume: 40 Issue: 8 Pages: 632-634
  • DOI: 10.1111/1346-8138.12203
  • Peer Reviewed
• [Journal Article] Down-regulation of miR-223 contributes to the formation of Gottron's papules in dermatomyositis via the induction of PKCε (2013)
  • Author(s): Inoue K, Jinnin M, Yamane K, Makino T, Kajihara I, Makino K, Honda N, Nakayama W, Fukushima S, Ihn H
  • Journal Title: Eur J Dermatol Volume: 23 Pages: 160-167
  • Peer Reviewed
• [Journal Article] The downregulation of microRNA let-7a contributes to the excessive expression of type I collagen in systemic and localized scleroderma. (2013)
  • Author(s): Makino K, Jinnin M, Hirano A, Yamane K, Eto M, Kusano T, Honda N, Kajihara I, Makino T, Sakai K, Masuguchi S, Fukushima S, Ihn H.
  • Journal Title: Journal of Immunology Volume: 190 Issue: 8 Pages: 3905-3915
  • DOI: 10.4049/jimmunol.1200822
  • Peer Reviewed