Elucidation of the pathogenic mechanism of IgA nephropathy through identification and functional analysis of the receptor for the insufficient glycosylated IgA molecules

2011 Fiscal Year Final Research Report

• Project/Area Number: 20390234
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Niigata University
• Principal Investigator: NARITA Ichiei 新潟大学, 医歯学系, 教授 (20272817)
• Co-Investigator(Kenkyū-buntansha): SAKATSUME Minoru 新潟大学, 医歯学系, 准教授 (70334662) ; KANEKO Yoshikatsu 新潟大学, 医歯学総合病院, 助教 (80444157)
• Project Period (FY): 2008 – 2011
• Keywords: IgA腎症 / 糖鎖不全 / 慢性糸球体腎炎 / メサンギウム細胞 / 受容体 / インテグリン / コラーゲン

Research Abstract

IgA nephropathy is characterized by mesangial deposition of IgA1 and galactose-deficient IgA1 is assumed to play a pathogenic role. However, the identity of the receptor for IgA1 is still controversial. Hence, the aim of this study was to explore the receptor for galactose-deficient IgA1. Human monoclonal IgA1 was treated with exoglycosidase and FITC-conjugated galactose-deficient IgA1 was used as a probe to detect the receptor in cultured human mesangial cells. According to comprehensive gene expression analysis, we revealed that galactose-deficient IgA1-collagen complex formation would be proposed as one of the candidate mechanisms of IgA1 deposition and proliferative signal transduction via integrinα2/β1 heterodimer in human mesangial cells.

Research Products

• [Journal Article] Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes (2012)
  • Author(s): Ogasawara S, Hosojima M, Kaseda R, Kabasawa H, Yamamoto-Kabasawa K, Kurosawa H, Sato H, Iino N, Takeda T, Suzuki Y, Narita I, Yamagata K, Tomino Y, Gejyo F, Hirayama Y, Sekine S, Saito A.
  • Journal Title: Diabetes Care Volume: (in press)
  • Peer Reviewed
• [Journal Article] A case of MPO-and PR3-ANCA-positive hypertrophic cranial pachymeningitis with elevated serum IgG4 (2012)
  • Author(s): Iguchi A, Wada Y, Kobayashi D, Sato H, Oyama T, Nakatsue T, Murakami S, Kuroda T, Nakano M, Narita I.
  • Journal Title: Mod Rheumatol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Integrin alpha1/beta1 and alpha2/beta1 as a receptor for IgA1 inhuman glomerular mesangial cells in Ig Anephropathy (2012)
  • Author(s): Kaneko Y, Otsuka T, Tsuchida Y, Gejyo F, Narita I.
  • Journal Title: Int Immunol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Light-microscopic characteristics of IgG4-related tubulointerstitial nephritis : distinction fromnon-IgG4-related tubulointerstitial nephritis (2012)
  • Author(s): Yoshita K, Kawano M, Mizushima I, HaraS, Ito Y, Imai N, Ueno M, Nishi S, Nomura H, Narita I, Saeki T.
  • Journal Title: Nephrol Dial Transplant Volume: (in press)
  • Peer Reviewed
• [Journal Article] Quantitative Histological Analysis of SM22 alpha(Transgelin) in an Adriamycin-Induced Focal Segmental Glomerulosclerosis Model (2011)
  • Author(s): Wang X, Sakatsume M, Sakamaki Y, Inomata S, Yamamoto T, Narita I
  • Journal Title: Nephron Exp Nephrol Volume: 120 Pages: e1-e11
  • Peer Reviewed
• [Journal Article] The effect of renal administration of a selective cyclooxygenase-2 inhibitor or stable prostaglandin I(2) analog on the progression of sclerotic glomerulonephritis in rats (2011)
  • Author(s): Nozawa Y, Sato A, Piao H, Morioka T, Narita I, Oite T
  • Journal Title: Clin Exp Nephrol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Weight gain after 20 yearsof age is associated with prevalence ofchronic kidney disease (2011)
  • Author(s): Wakasugi M, Narita I, Iseki K, Moriyama T, Yamagata K, Tsuruya K, Yoshida H, Fujimoto S, Asahi K, Kurahashi I, Ohashi Y, Watanabe T.
  • Journal Title: Clin Exp Nephrol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Megalin isdownregulated via LPS-TNF-alpha-ERK1/2 signaling pathway in proximal tubule cells (2011)
  • Author(s): Takeyama A, Sato H, Soma-Nagae T, Kabasawa H, Suzuki A, Yamamoto-Kabasawa K, Hosojima M, Kaneko R, Higuchi F, Kaseda R, Ogasawara S, Narita I, Saito A
  • Journal Title: Biochem Biophys Res Commun Volume: 407 Pages: 108-112
  • Peer Reviewed
• [Journal Article] Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy : potential role in mesangial matrix expansion (2011)
  • Author(s): Ikezumi Y, Suzuki T, Karasawa T, Hasegawa H, Yamada T, Imai N, Narita I, Kawachi H, Polkinghorne KR, Nikolic-Paterson DJ, Uchiyama M
  • Journal Title: Histopathology Volume: 58 Pages: 198-210
  • Peer Reviewed
• [Journal Article] Injured kidney cells express SM22alpha(transgelin): Unique features distinct from alpha-smooth muscle actin(alphaSMA) (2011)
  • Author(s): Sakamaki Y, Sakatsume M, Wang X, Inomata S, Yamamoto T, Gejyo F, Narita I
  • Journal Title: Nephrology(Carlton) Volume: 16 Pages: 211-218
  • Peer Reviewed
• [Journal Article] Novel expression of claudin-5 in glomerular podocytes (2011)
  • Author(s): Koda R, Zhao L, Yaoita E, Yoshida Y, Tsukita S, Tamura A, Nameta M, Zhang Y, Fujinaka H, Magdeldin S, Xu B, Narita I, Yamamoto T
  • Journal Title: Cell Tissue Res Volume: 343 Pages: 637-648
  • Peer Reviewed
• [Journal Article] Membranoproliferative pattern of glomerular injury associated with complement component 9 deficiency due to Arg95Stop mutation (2011)
  • Author(s): Miura T, Goto S, Iguchi S, Shimada H, Ueno M, Nishi S, Narita I
  • Journal Title: Clin Exp Nephrol Volume: 15 Pages: 86-91
  • Peer Reviewed
• [Journal Article] Expression of SM22alpha(transgelin) in glomerular and interstitial renal injury (2011)
  • Author(s): Inomata S, Sakatsume M, Sakamaki Y, Wang X, Goto S, Yamamoto T, Gejyo F, Narita I
  • Journal Title: Nephron Exp Nephrol Volume: 117 Pages: e104-113
  • Peer Reviewed
• [Presentation] Genome-wide linkage scan of Japanese families with IgA nephropathy (2011)
  • Author(s): Goto S, Tsukaguchi H, Wada M, Narita I
  • Organizer: American Society of Nephrology Kidney Week 2011
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20111118-13
• [Presentation] Prolactin receptor was up-regulated in the proximal tubules of the kidney in the cardio-renal syndrome model mice (2011)
  • Author(s): Tsuchida Y, Kaneko Y, Saito A, Yamamoto S, Narita I
  • Organizer: American Society of Nephrology Kidney Week 2011
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20111108-13
• [Presentation] Symposium/Membrano proliferative glomerulonephritis (2011)
  • Author(s): Narita I
  • Organizer: Advancement in Treatment of Nephrotic Syndrome
  • Place of Presentation: Yokohama
  • Year and Date: 2011-06-14
• [Presentation] Integrinα2/β1 as a novel galactose-deficient IgA1receptor on Human mesangial cells (2011)
  • Author(s): Kaneko Y, Tsuchida Y, Narita I
  • Organizer: World Congress of Nephrology 2011
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2011-04-10
• [Book] Annual Review腎臓 (2012)
  • Author(s): 成田一衛, 他編
  • Total Pages: 231
  • Publisher: 中外医学社