The role of megalin in secondary hyerparathyroidism of uremia

• Project/Area Number: 24591235
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka City University
• Principal Investigator: IMANISHI Yasuo 大阪市立大学, 医学(系)研究科(研究院), 講師 (50326253)
• Co-Investigator(Kenkyū-buntansha): YAMAGATA Masayo 大阪大谷大学, 薬学部, 講師 (50454583)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 副甲状腺メガリン / メガリン / 副甲状腺 / ビタミンD受容体

Outline of Final Research Achievements

Megalin is a multiligand endocytotic receptor involving in the reabsorption of calcitriol and vitamin D binding protein in renal proximal tubules. Parathyroid glands also express megalin, however, little is known about its expressions and pathophysiological roles in hyperfunctioning parathyroid tumors. Its expression was observed in plasma membranes and cytoplasm in normal parathyroid glands. The expressions decreased in tumors with primary hyperparathyroidism and secondary hyperparathyroidism of uremia (SHPT) compared with strong expression in normal parathyroid glands. In SHPT, its expression was often particularly depressed in nodular areas, compared with adjacent diffuse hyperplasias. The reduced expression of both megalin and VDR may enhance vitamin D resistance and hyper-secretion of PTH from these tumors.

Research Products

• [Journal Article] Increased undercarboxylated osteocalcin/intact osteocalcin ratio in patients undergoing hemodialysis (2015)
  • Author(s): Nagata, Y., Inaba, M., Imanishi, Y., Okazaki, H., Yamada, S., Mori, K., Shoji, S., Koyama, H. and Okuno, S
  • Journal Title: Osteoporos Int Volume: 26 Issue: 3 Pages: 1053-61
  • DOI: 10.1007/s00198-014-2954-4
  • Peer Reviewed
• [Journal Article] Association between glycemic control and morning blood pressure surge with vascular endothelial dysfunction in type 2 diabetic patients. (2014)
  • Author(s): Yoda K, Inaba M, Hamamoto K, Yoda M, Tsuda A, Mori K, Yamada S, Emoto M, Koyama H, Imanishi Y
  • Journal Title: Diabetes Care Volume: 37 Issue: 3 Pages: 644-650
  • DOI: 10.2337/dc13-1102
  • Peer Reviewed
• [Journal Article] Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression. (2014)
  • Author(s): Ochi A, Mori K, Emoto M, Nakatani S, Morioka T, Motoyama K, Fukumoto S, Imanishi Y, Koyama H, Ishimura E, Inaba M
  • Journal Title: PLoS One Volume: 9 Issue: 2 Pages: e88704-e88704
  • DOI: 10.1371/journal.pone.0088704
  • Peer Reviewed
• [Journal Article] Strategy of operative treatment of hyperparathyroidism using US scan and (99m)Tc-MIBI SPECT/CT (2014)
  • Author(s): Noda S, Onoda N, Kashiwagi S, Kawajiri H, Takashima T, Ishikawa T, Yoshida A, Higashiyama S, Kawabe J, Imanishi Y, Tahara H, Inaba M, Osawa M, Hirakawa K
  • Journal Title: Endocr J Volume: 61 Pages: 225-230
  • NAID: 130004443938
  • Peer Reviewed
• [Journal Article] Association between glycemic control and morning blood pressure surge with vascular endothelial dysfunction in type 2 diabetic patients. (2014)
  • Author(s): Yoda K, Inaba M, Hamamoto K, Yoda M, Tsuda A, Mori K, Yamada S, Emoto M, Koyama H, Imanishi Y
  • Journal Title: Diabetes Care Volume: 37 Pages: 644-650
  • Peer Reviewed
• [Journal Article] Undercarboxylated osteocalcin does not correlate with insulin resistance as assessed by euglycemic hyperinsulinemic clamp technique in patients with type 2 diabetes mellitus. (2013)
  • Author(s): Mori K, Emoto M, Motoyama K, Lee E, Yamada S, Morioka T, Imanishi Y, Shoji T, Inaba M
  • Journal Title: Diabetol Metab Syndr Volume: 4 Issue: 1 Pages: 53-53
  • DOI: 10.1186/1758-5996-4-53
  • Peer Reviewed
• [Journal Article] Matrix extracellular phosphoglycoprotein is expressed in causative tumors of oncogenic osteomalacia. (2012)
  • Author(s): Imanishi Y, Hashimoto J, Ando W, Kobayashi K, Ueda T, Nagata Y, Miyauchi A, Koyano HM, Kaji H, Saito T, Oba K, Komatsu Y, Morioka T, Mori K, Miki T, Inaba M
  • Journal Title: J Bone Miner Metab Volume: 30 Issue: 1 Pages: 93-99
  • DOI: 10.1007/s00774-011-0290-8
  • NAID: 10031168757
  • Peer Reviewed
• [Journal Article] Impact of atherosclerosis on the relationship of glycemic control and mortality in diabetic patients on hemodialysis. (2012)
  • Author(s): Inaba M, Maekawa K, Ishimura E, et al.
  • Journal Title: Clin Nephrol Volume: 78 Issue: 10 Pages: 273-280
  • DOI: 10.5414/cn106940
  • Peer Reviewed
• [Journal Article] Higher serum bone alkaline phosphatase as a predictor of mortality in male hemodialysis patients. (2012)
  • Author(s): Kobayashi I, Shidara K, Okuno S, Yamada S, Imanishi Y, Mori K, Ishimura E, Shoji S, Yamakawa T, Inaba M
  • Journal Title: Life Sci Volume: 90 Issue: 5-6 Pages: 212-218
  • DOI: 10.1016/j.lfs.2011.11.006
  • Peer Reviewed
• [Journal Article] Impaired Response of FGF-23 to Oral Phosphate in Patients with Type 2 Diabetes: A Possible Mechanism of Atherosclerosis. (2012)
  • Author(s): Yoda K, Imanishi Y, Yoda M, Mishima T, Ichii M, Yamada S, Mori K, Emoto M, Inaba M
  • Journal Title: J Clin Endocrinol Metab Volume: 97 Issue: 11 Pages: E2036-E2043
  • DOI: 10.1210/jc.2012-2024
  • Peer Reviewed
• [Journal Article] Poor muscle quality as a predictor of high mortality independent of diabetes in hemodialysis patients. (2012)
  • Author(s): Yoda M, Inaba M, Ishimura E, et al.
  • Journal Title: Biomed Pharmacother Volume: 66 Issue: 4 Pages: 266-270
  • DOI: 10.1016/j.biopha.2011.11.001
  • Peer Reviewed
• [Presentation] Improvement of carotid wall thickness by teriparatide: intervention on vicious bone-vascular axis (2014)
  • Author(s): Yasuo Imanishi, Maki Yoda, Yuki Nagata, Masaya Ohara, Kouichirou Yoda, Shinsuke Yamada, Katsuhito Mori, Masaaki Inaba
  • Organizer: IOF Regionals 5th Asia-Pacific Osteoporosis Meeting
  • Place of Presentation: Taipei International Convention Centre (Chinese Taipei)
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] Involvement of impaired FGF23 secretion in the acceleration of atherosclerosis in CKD with diabetes mellitus (2014)
  • Author(s): Imanishi Y, Inaba M
  • Organizer: 8th International Congress on Uremia Research and Toxicity
  • Place of Presentation: Okinawa Convention Center
  • Invited
• [Presentation] 慢性腎臓病(CKD)と骨・カルシウム・リン代謝 (2014)
  • Author(s): 今西康雄、稲葉雅章
  • Organizer: 第23回臨床内分泌代謝Update
  • Place of Presentation: 名古屋国際会議場
  • Invited
• [Presentation] Ameliorated dual abnormalities of megalin and NaPi-IIc expressions in proximal renal tubules by oral prednisolone therapy in a case of anti-mitochondrial antibodies-M2 positive tubulointerstitial nephritis with Fanconi syndrome (2012)
  • Author(s): Ikue Kobayashi, Yasuo Imanishi, Masafumi Kurajoh, Yuki Nagata, Masayo Yamagata, Masanori Emoto, Toshimi Michigami, Eiji Ishimura, Masaaki Inaba
  • Organizer: IL ERA-EDTA Congress
  • Place of Presentation: Paris, France
• [Presentation] Attenuated megalin expression in hyperfunctioning parathyroid glands – possible role of vitamin D signaling (2012)
  • Author(s): Nagata Y, Imanishi Y, Yamagata M, Kobayashi I, Ishii A, Michigami T, Yukimura T, Arnold A, Inaba M
  • Organizer: 1st Asia-Pacific Bone and Mineral Research Meeting with the ANZBMS 22nd Annual Scientific Meeting
  • Place of Presentation: Perth, Western Australia
• [Presentation] The expression of CD73 and osteoblast/osteocyte specific genes in causative tumors of oncogenic osteomalacia (2012)
  • Author(s): Yuki Nagata, Yasuo Imanishi, Jun Hashimoto, Akimitsu Miyauchi, Hiroshi Kaji, Katsuhito Mori, Keisuke Kobayashi, Masaaki Inaba
  • Organizer: ASBMR 34th Annual Meeting
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Relationship between Marrow Adipocyte and Aortic Calcification in Chronic Dialysis Patients (2012)
  • Author(s): Aiji Yajima, Yasuo Imanishi, Masaaki Inaba, Kosaku Nitta
  • Organizer: Renal Week 2012
  • Place of Presentation: San Diego, California
• [Presentation] Impaired FGF-23 increment to oral phosphate loading in patients with type 2 diabetes - possible mechanism of atherosclerosis - (2012)
  • Author(s): Masaaki Inaba, Yasuo Imanishi, Kouichiro Yoda, Masanori Emoto
  • Organizer: International Diabetes Federation Western Pacific Region Congress (9th IDF-WPR) & 4th Scientific Meeting of Asian Association for Study of Diabetes (4th AASD)
  • Place of Presentation: Kyoto, Japan
  • Invited
• [Presentation] 重症骨粗鬆症患者において、睡眠の質の低下と精神的なQOLが相関する (2012)
  • Author(s): 今西康雄、後藤仁志
  • Organizer: 第54回日本老年医学会学術集会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] CKDにおけるCa,P調節機構のupdate (2012)
  • Author(s): 今西康雄、奥野仙二、絵本正憲、稲葉雅章
  • Organizer: 第57回日本透析医学会学術集会・総会
  • Place of Presentation: 京王プラザホテル札幌
• [Presentation] 副甲状腺ホルモン分泌調節機構とその異常 (2012)
  • Author(s): 今西康雄、山形雅代、稲葉雅章
  • Organizer: 第30回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル
  • Invited
• [Presentation] ビタミンDシグナルの異常と副甲状腺機能亢進症 (2012)
  • Author(s): 今西康雄、山形雅代、絵本正憲、稲葉雅章
  • Organizer: 第30回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル
  • Invited
• [Presentation] テリパラチド投与における骨代謝マーカーの変化について (2012)
  • Author(s): 今西康雄、三木隆己、稲葉雅章
  • Organizer: 第32回日本骨形態計測学会
  • Place of Presentation: 大阪国際会議場
  • Invited
• [Presentation] ヒト腸骨生検の骨組織像 (2012)
  • Author(s): 伊藤明美、矢島愛治、矢嶋伊吹、今西康雄
  • Organizer: 第32回日本骨形態計測学会
  • Place of Presentation: 大阪国際会議場
  • Invited
• [Presentation] 腫瘍性骨軟化症における原因腫瘍摘出後の骨代謝マーカーの推移について (2012)
  • Author(s): 今西康雄、永田友貴、小原正也、小林郁恵、山田真介、三木隆己、稲葉雅章
  • Organizer: 第32回日本骨形態計測学会
  • Place of Presentation: 大阪国際会議場