Role of calcium/calmodulin kinase IV on podocyte function in lupus nephritis

• Project/Area Number: 24790999
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Nagasaki University
• Principal Investigator: ICHINOSE Kunihiro 長崎大学, 医歯(薬)学総合研究科, 助教 (60437895)
• Co-Investigator(Kenkyū-buntansha): KAWAKAMI Astushi 長崎大学, 大学院・医歯薬学総合研究科展開医療科学講座(第一内科), 教授 (90325639) ; NAKAMURA Hideki 長崎大学, 病院第一内科, 講師 (10437832) ; IWAMOTO Naoki 長崎大学, 病院第一内科, 助教 (80437897)
• Co-Investigator(Renkei-kenkyūsha): KOGA Tomohiro 長崎大学, 病院第一内科, 助教 (90537284)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 全身性エリテマトーデス / ループス腎炎 / ポドサイト / CaMKIV / CD86 / 国際情報交換、アメリカ

Research Abstract

T cell from patients with systemic lupus erythematosus display increased expression of calcium/calmodulin kinase IV (CaMKIV). CaMKIV expression was found increased in podocytes of Lupus nephritis(LN) kidney biopsy specimens. The levels of nephrin and CaMKIV correlated in an inverse manner. Interestingly, culture of AB8/13 podocytes in the presence of IgG from LN sera led to 1.5-fold increase in the expression of CaMKIV mRNA. Gene array analysis revealed that the expression of genes related to the cell activation including CaMKIV increased significantly (P<0.05) and the regulation of neural precursor cell proliferation decreased significantly (P<0.01) in podocytes treated with IgG from LN patients. Our data demonstrate increased expression of CaMKIV in LN podocytes which may represent the result of exposure to IgG. We suspect that increased CaMKIV expression may contribute to the inability of podocytes to maintain the integrity of glomerular basement membrane in LN patients.

Research Products

• [Journal Article] A case of microscopic polyangiitis in an elderly patient presenting predominantly with cholecystitis successfully treated with mizoribine. (2013)
  • Author(s): Ichinose K, Iwanaga N, Okada A, Tamai M, Yamasaki S, Nakamura H, Origuchi T, Kawakami A.
  • Journal Title: Mod Rheumatol. Volume: Feb.9
  • DOI: 10.1007/s10165-013-0841-z
  • Peer Reviewed
• [Journal Article] Brief report: increased expression of a short splice variant of CTLA-4 exacerbates lupus in MRL/lpr mice. (2013)
  • Author(s): Ichinose K, Zhang Z, Koga T, Juang YT, Kis-Toth K, Sharpe AH, Kuchroo V, Crispin JC, Tsokos GC.
  • Journal Title: Arthritis Rheum. Volume: 65(3) Issue: 3 Pages: 764-9
  • DOI: 10.1002/art.37790
  • Peer Reviewed
• [Journal Article] HTLV-I virological and histopathological analysis in two cases of anti-centromere-antibody-seropositive Sjögren's syndrome. (2013)
  • Author(s): Hideki Nakamura
  • Journal Title: Modern Rheumatology Volume: 23 Issue: 1 Pages: 133-139
  • DOI: 10.1007/s10165-012-0641-x
  • Peer Reviewed
• [Journal Article] TLR3-mediated apoptosis and activation of phosphorylated Akt in the salivary gland epithelial cells of primary Sjögren’s syndrome patients. (2013)
  • Author(s): Hideki Nakamura
  • Journal Title: Rheumatology International Volume: 33 Issue: 2 Pages: 441-450
  • DOI: 10.1007/s00296-012-2381-9
  • NAID: 120006985741
  • Peer Reviewed
• [Journal Article] Calcium/calmodulin-dependent protein kinase IV suppresses IL-2 production and regulatory T cell activity in lupus. (2012)
  • Author(s): Koga T, Ichinose K, Mizui M, Crispin JC, Tsokos GC.
  • Journal Title: J Immunol. Volume: 189(7) Issue: 7 Pages: 3490-6
  • DOI: 10.4049/jimmunol.1201785
  • Peer Reviewed
• [Journal Article] An elderly patient with chronic active Epstein-Barr virus infection with mixed cryoglobulinemia and review of the literature. (2012)
  • Author(s): Ichinose K, Origuchi T, Tashiro N, Kawashiri SY, Iwamoto N, Fujikawa K, Aramaki T, Arima K, Tamai M, Yamasaki S, Nakamura H, Moriuchi H, Kawakami A.
  • Journal Title: Mod Rheumatol. Volume: Aug.16 Issue: 5 Pages: 1022-1028
  • DOI: 10.1007/s10165-012-0731-9
  • NAID: 10031201164
  • Peer Reviewed
• [Journal Article] A case of cutaneous polyarteritis nodosa with elevated serum interleukin-6 levels complicated by leg arterial stenosis and destructive arthropathy of the left ankle. (2012)
  • Author(s): Horai Y, Tokuyama A, Sumiyoshi R, Nakashima Y, Suzuki T, Okada A, Kawashiri SY, Ichinose K, Izumi Y, Miyashita T, Tamai M, Yamasaki S, Nakamura H, Hayashi T, Origuchi T, Kawakami A.
  • Journal Title: Mod Rheumatol. Volume: Sep.13
  • DOI: 10.1007/s10165-012-0753-3
  • Peer Reviewed
• [Journal Article] Takayasu arteritis developing during treatment of ulcerative colitis with infliximab. (2012)
  • Author(s): Horai Y, Satoru O, Lapalme-Remis S, Sumiyoshi R, Nakashima Y, Suzuki T, Okada A, Kawashiri SY, Ichinose K, Tamai M, Yamasaki S, Nakamura H, Takeshima F, Origuchi T, Kawakami A.
  • Journal Title: Mod Rheumatol. Volume: Jun.21 Issue: 3 Pages: 572-576
  • DOI: 10.1007/s10165-012-0684-z
  • NAID: 10031175919
  • Peer Reviewed
• [Presentation] ループス腎炎におけるCalcium/calmodulin dependent kinase protein type IV のポドサイト機能に対する影響(第2 報) (2014)
  • Author(s): 一瀬邦弘, 牛草健, 梅田雅孝, 中島好一, 鈴木貴久, 寶來吉朗, 岡田覚丈, 川㞍真也, 岩本直樹, 玉井慎美, 中村英樹, 折口智樹, 川上純
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京・グランドプリンス新高輪本館及び国際館パミール
• [Presentation] ループス腎炎におけるCalcium/calmodulin dependent kinase protein type IVのポドサイト機能に対する影響(第2報) (2014)
  • Author(s): 一瀬邦弘、牛草健、,高谷亜由子、西野文子、中島好一、鈴木貴久、寶來吉朗、川尻真也、岩本直樹、玉井慎美、中村英樹、折口智樹、川上純
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京・グランドプリンスホテル新高輪本館及び国際館パミール
• [Presentation] Role of calcium/calmodulin kinase IV on podocyte function in lupus nephritis (2013)
  • Author(s): Kunihiro Ichinose, Takeshi Ushigusa, Tomohiro Koga, George C.Tsokos, Atsushi Kawakami
  • Organizer: The ACR/ARHP 2013 Annual Meeting
  • Place of Presentation: San Diego, CA, USA
• [Presentation] ループス腎炎におけるCalcium/calmodulin dependent kinase protein type IV のポドサイト機能に対する影響 (2013)
  • Author(s): 一瀬邦弘, 牛草健, 川上純
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京・東京国際フォーラム
• [Presentation] Role of calcium/calmodulin kinase IV on podocyte function in lupus nephritis (2013)
  • Author(s): Kunihiro Ichinose, Takeshi Ushigusa, Tomohiro Koga, George C.Tsokos, Atsushi Kawakami
  • Organizer: Immunology 2013
  • Place of Presentation: Honolulu, HI, USA
• [Presentation] ループス腎炎におけるCalcium/calmodulin dependent kinase protein type IV のポドサイト機能に対する影響 (2013)
  • Author(s): 一瀬邦弘, 牛草健, 梅田雅孝, 中島好一, 鈴木貴久, 寶來吉朗, 岡田覚丈, 川㞍真也, 岩本直樹, 玉井慎美, 中村英樹, 折口智樹, 川上純
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 京都・国立京都国際会館
• [Presentation] ループス腎炎 ループス腎炎におけるCalcium/calmodulin dependent kinase protein type IVのポドサイト機能に対する影響 (2013)
  • Author(s): 一瀬邦弘、牛草健、梅田雅孝、中島好一、鈴木貴久、寶來吉朗、岡田覚丈、川尻真也、岩本直樹、玉井慎美、中村英樹、折口智樹、川上純
  • Organizer: 第57回日本リウマチ学会総会・学術集会
  • Place of Presentation: 京都・国立京都国際会館
• [Presentation] ループス腎炎におけるCalcium/calmodulin dependent kinase protein type IVのポドサイト機能に対する影響 (2013)
  • Author(s): 一瀬邦弘、牛草健、川上純
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京・東京国際フォーラム
• [Presentation] Role of calcium/calmodulin kinase IV on podocyte function in lupus nephritis (2013)
  • Author(s): Kunihiro Ichinose, Takeshi Ushigusa, Tomohiro Koga, Geroge C. Tsokos, Atushi Kawakami
  • Organizer: IMMUNOLOGY 2013
  • Place of Presentation: Honolulu, HI, USA
• [Presentation] Inhibition of Calcium/calmodulin-dependent protein kinase IV suppresses the autoimmunity in lupus-prone mice (2012)
  • Author(s): Kunihiro Ichinose, Atsushi Kawakami and George C. Tsokos
  • Organizer: Immunology 2012
  • Place of Presentation: Boston, USA
• [Presentation] Inhibition of Calcium/calmodulin-dependent protein kinase IV suppresses the autoimmunity in lupus-prone mice (2012)
  • Author(s): Kunihiro Ichinose, Atsushi Kawakami and George C. Tsokos
  • Organizer: ACR/ARHP 2012
  • Place of Presentation: Washington, DC, USA.
• [Presentation] ループス腎炎とメサンギウム細胞増殖におけるCalcium/calmodulin-dependent protein kinase type IVの重要性 (2012)
  • Author(s): 一瀬 邦弘,川上 純, George C. Tsokos
  • Organizer: 第56回 日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] 高齢発症の慢性活動性EBウイルス感染症に混合型クリオグロブリン血症を合併した一例 (2012)
  • Author(s): 一瀬邦弘、川尻真也、玉井慎美、山崎聡士、中村英樹、折口智樹、川上純
  • Organizer: 第56回 日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] ループス腎炎のメサンギウム細胞におけるCalcium/calmodulin-dependent protein kinase type IVの役割 (2012)
  • Author(s): 一瀬邦弘、川上純、George C. Tsokos
  • Organizer: 第40回日本臨床免疫学会総会：2012
  • Place of Presentation: 東京