Regulation of intracellular Ca2+ concentration in epidermal keratinocytes: Study for coordination in three calcium pumps and their roles for epidermal differentiation

• Project/Area Number: 23791298
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Kurume University
• Principal Investigator: HAMADA Takahiro 久留米大学, 医学部, 講師 (40320204)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 遺伝学 / 遺伝子 / ゲノム / 単一遺伝子病 / 遺伝性皮膚疾患 / カルシウムポンプ / 皮膚病理学

Research Abstract

Hailey-Hailey disease (HHD) and Darier disease (DD) are caused by mutations in the genes encoding the intracellular calcium pumps. In this study, we investigated the roles for intracellular Ca2+ homeostasis and epidermal differentiation in these calcium pumps, using cultured epidermal keratinocytes (KCs) derived from patients with HHD and DD. HHD KCs revealed the altered response of Ca2+ release from intracellular stores to ATP stimulation, but not by constitutive elevation of cytoplasmic Ca2+. The expressions of several calcium-binding proteins and epidermal differentiation-mediated proteins (e.g.calmodulin-like 5 and loricrin) were increased in HHD KCs compared to normal control.

Research Products

• [Journal Article] A d Late-onset Darier's disease due to a novel missense mutation in the ATP2A2 gene: ifferent missense mutation affecting the same codon has been previously reported in acrokeratosis verruciformis. (2013)
  • Author(s): Ueo D, Hamada T, Hashimoto T, Hatano Y, Okamoto O, Fujiwara S.
  • Journal Title: J Dermatol Volume: 40 Issue: 4 Pages: 280-281
  • DOI: 10.1111/1346-8138.12058
  • Peer Reviewed
• [Journal Article] Anti-alpha-2-macroglobulin-like-1 Autoantibodies are Detected Frequently and may be Pathogenic in Paraneoplastic Pemphigus. (2013)
  • Author(s): Hamada T, Karashima T,Nakama T, Furumura M, Ohata C, Kawakami T, Schepens I, BorradoriL,HashimotoT
  • Journal Title: J Invest Dermatol Volume: 50(4) Issue: 4 Pages: 13-13
  • DOI: 10.1111/j.1365-4632.2010.04702.x
  • Peer Reviewed
• [Journal Article] How do keratinizing disorders and blistering disorders overlap (2013)
  • Author(s): Hamada T, Tsuruta D, Fukuda S, Ishii N, Teye K, Numata S, Dainichi T, Karashima T, Ohata C, Furumura M,Hashimoto T.
  • Journal Title: Exp Dermatol Volume: 22 Issue: 2 Pages: 83-87
  • DOI: 10.1111/exd.12021
  • Peer Reviewed
• [Journal Article] Anti-alpha-2-macroglobulin-like-1 Autoantibodies are Detected Frequently and may be Pathogenic in Paraneoplastic Pemphigus. (2013)
  • Author(s): Numata S, Teye K, Tsuruta D, Sogame R, Ishii N, Koga H, Natsuaki Y, Tsuchisaka A, Hamada T, Karashima T,Nakama T, Furumura M, Ohata C, Kawakami T, Schepens I, Borradori L, Hashimoto T.
  • Journal Title: J Invest Dermatol Volume: Epub ahead of print Issue: 7 Pages: 1785-1793
  • DOI: 10.1038/jid.2013.65
  • Peer Reviewed
• [Journal Article] Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2-based swapped molecules (2012)
  • Author(s): Ohyama, B.
  • Journal Title: J Invest Dermatol Volume: 132 Issue: 4 Pages: 1158-1168
  • DOI: 10.1038/jid.2011.448
  • Peer Reviewed
• [Journal Article] Interaction of plectin and intermediate filaments. (2012)
  • Author(s): Karashima T, Tsuruta D, Hamada T, Ishii N, Ono F, Hashikawa K, Ohyama B, Natsuaki Y, Fukuda S, Koga H,Sogame R, Nakama T, Dainichi T, Hashimoto T.
  • Journal Title: J Dermatol Sci Volume: 66 Issue: 1 Pages: 44-50
  • DOI: 10.1016/j.jdermsci.2012.01.008
  • Peer Reviewed
• [Journal Article] Novel adenosine triphosphate (ATP)-binding cassette, subfamily A, member 12 (ABCA12) mutations associated with congenital ichthyosiform erythroderma. Br (2012)
  • Author(s): Fukuda S, Hamada T, Ishii N, Sakaguchi S, Sakai K, Akiyama M, Shimizu H, Masuda K, Izu K, Teye K, Tsuruta D, Karashima T, Nakama T, Yasumoto S, Hashimoto T.
  • Journal Title: J Dermatol Volume: 166(1) Issue: 1 Pages: 218-221
  • DOI: 10.1111/j.1365-2133.2011.10516.x
  • Peer Reviewed
• [Journal Article] Novel adenosine triphosphate (ATP)-binding cassette, subfamily A, member 12 (ABCA12) mutations associated with congenital ichthyosiform erythroderma. (2012)
  • Author(s): Fukuda S et al.
  • Journal Title: Br J Dermatol Volume: 166(1) Pages: 218-221
  • Peer Reviewed
• [Journal Article] Atypical epidermolysis bullosa simplex with a missense keratin 14 mutation p.Arg125Cys. (2011)
  • Author(s): Tsuruta D, Sowa J, Tateishi C, Obase Y, Tsubura A, Fukumoto T, Ishii M, Kobayashi H, Sakaguchi S, Hashimoto T, Hamada T.
  • Journal Title: J Dermatol Volume: 38(12) Issue: 12 Pages: 1177-1179
  • DOI: 10.1111/j.1346-8138.2011.01302.x
  • NAID: 10031147165
  • Peer Reviewed
• [Journal Article] Sawamura D, Hashimoto T. Exon 87 skipping of the COL7A1 gene in dominant dystrophic epidermolysis bullosa. (2011)
  • Author(s): Koga H, Hamada T, Ishii N, Fukuda S, Sakaguchi S, Nakano H, Tamai K
  • Journal Title: J Dermatol Volume: 38(5) Issue: 5 Pages: 489-492
  • DOI: 10.1111/j.1346-8138.2010.01008.x
  • Peer Reviewed
• [Journal Article] Exon 87 skipping of the COL7A1 gene in dominant dystrophic epidermolysis bullosa. (2011)
  • Author(s): Koga H et al.
  • Journal Title: J Dermatol Volume: 38(5) Pages: 489-492
  • Peer Reviewed
• [Journal Article] Missense mutation at the helix termination region in the 2B domain of keratin 14 in a Japanese family with epidermoliysis bullosa simplex, generalized other. (2011)
  • Author(s): Kaneko S et al.
  • Journal Title: Int J Dermatol Volume: 50(4) Pages: 436-438
  • Peer Reviewed
• [Presentation] Studies of cultured Hailey-Hailey disease keratinocytes revealed pathogenic role of the mutations and novel mechanism in Ca2+ homeostasis (2012)
  • Author(s): Matsuda M, Hamada T, Ishii N, Sakaguchi S, Murai Y, Ohata C, Furumura M, Tanaka E, Hashimoto T.
  • Organizer: The 36th annual meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa
• [Presentation] Hailey-Hailey病30家系におけるATP2C1遺伝子変異と細胞内カルシウム動態や角化に関与する遺伝子群の発現について (2012)
  • Author(s): 松田光弘、濱田尚宏、坂口幸子、石井文人、辛島正志、古村南夫、橋本隆
  • Organizer: 第19回分子皮膚科学フォーラム
  • Place of Presentation: 青森市
• [Presentation] Studies of cultured Hailey-Hailey disease keratinocytes revealed pathogenic role of the mutations and novel mechanism in Ca2+ homeostasis. (2012)
  • Author(s): 1） Matsuda M, Hamada T, Ishii N, Sakaguchi S, Murai Y, Ohata C, Furumura M, Tanaka E, Hashimoto T.
  • Organizer: The 37th annual meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa
  • Invited
• [Presentation] Impaired innate immunity to HSV in Hailey-Hailey disease is caused by TLR9 defect through abnormal cytoplasmic Ca2+ signalling (2011)
  • Author(s): Hamada T, Ogawa M, Ishii N, Ono F, Matsuda M, Sakaguchi S, Karashima T, Nakama T, Dainichi T, Tsuruta D, Yasumoto S, Hashimoto T.
  • Organizer: The 36th annual meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Kyoto
• [Presentation] Impaired innate immunity to HSV in Hailey-Hailey disease is caused by TLR9 defect through abnormal cytoplasmic Ca2+ signalling. (2011)
  • Author(s): Hamada T
  • Organizer: The 36th annual meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Kyoto