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The role of circadian abnormalities in salivary gland disorders

Research Project

Project/Area Number 18K09922
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57080:Social dentistry-related
Research InstitutionNihon University

Principal Investigator

BHAWAL Ujjal  日本大学, 松戸歯学部, 講師 (50433339)

Co-Investigator(Kenkyū-buntansha) 田中 ゆり子  東邦大学, 医学部, 講師 (40396685)
佐藤 冬樹  静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (60400131)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords加齢 / 唾液腺 / DNAマイクロアレイ / microRNAアレイ / 体内時計 / microRNAマイクロアレイ / 時計遺伝子 / 老化 / シェーグレン症候群
Outline of Final Research Achievements

Submandibular glands of 3-month-old and 24-month-old C57BL/6 mice were used for analysis of genes and miRNAs using DNA microarrays and miRNA arrays in combination with Gene Spring and Ingenuity Pathways Analysis. The regulatory transcription factors of aging are involved in the regulation of miR-30c-1-3p, miR-34a-5p, miR-92a-3p, miR-181a-5p, and miR-550a-3p. The 3'UTR activity of the DEC1 was increased with aging but it was alleviated in the mutation of the target miRNA binding site in the luciferase reporter assay. In addition, DEC1 expression plasmid was forcibly suppressed the E-cadherin transcription activity in a dose-dependent manner. Furthermore, Chromatin immunoprecipitation (ChIP assay) confirmed that DEC1 regulates E-cadherin. Collectively, our data suggest a regulatory effect of DEC1 in E-cadherin-mediated salivary gland function.

Academic Significance and Societal Importance of the Research Achievements

高齢化に伴う唾液分泌障害者の増加は歯周病のリスクを上げるだけではなく、嚥下障害や誤嚥性肺炎の発症を招くなど、全身にも悪影響を与える。唾液腺樹状細胞が唾液腺健康維持に重要な働きをしていることが明らかになり、シェーグレン症候群や加齢など唾液腺疾患の発症機序の解明にも大きく貢献することが期待されている。本研究において、唾液腺の老化のメカニズムを解明するだけでなく、唾液分泌障害の診断や対処法の確立に役立つと思われる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (50 results)

All 2021 2020 2019 2018

All Journal Article (15 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 15 results,  Open Access: 10 results) Presentation (35 results) (of which Int'l Joint Research: 12 results,  Invited: 5 results)

  • [Journal Article] A deficiency of Dec2 triggers periodontal inflammation and pyroptosis2021

    • Author(s)
      Oka S, Li X, Sato F, Zhang F, Tewari N, Kim IS, Zhong L, Hamada N, Makishima M, Liu Y, Bhawal UK
    • Journal Title

      Journal of Periodontal Research

      Volume: 00 Issue: 3 Pages: 1-9

    • DOI

      10.1111/jre.12849

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Loss of Dec1 prevents autophagy in inflamed periodontal ligament fibroblast2021

    • Author(s)
      Oka S, Li X, Zhang F, Tewari N, Kim IS, Chen C, Zhong L, Hamada N, Oi Y, Makishima M, Liu Y, Bhawal UK
    • Journal Title

      Molecular Biology Reports

      Volume: 48(2) Issue: 2 Pages: 1423-1431

    • DOI

      10.1007/s11033-021-06162-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dec2 attenuates autophagy in inflamed periodontal tissues2021

    • Author(s)
      Oka S, Li X, Sato F, Zhang F, Tewari N, Chen C, Zhong L, Makishima M, Liu Y, Bhawal UK
    • Journal Title

      Immunity, Inflammation and Disease

      Volume: 9(1) Issue: 1 Pages: 265-273

    • DOI

      10.1002/iid3.389

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti-aging effects of Korean Red Ginseng (KRG) in differentiated embryo chondrocyte (DEC) knockout mice2021

    • Author(s)
      Nam YH, Jeong SY, Kim YH, Rodriguez I, Nuankaew W, Bhawal UK, Hong BN, Kang TH
    • Journal Title

      Journal of Ginseng Research

      Volume: 45(1) Issue: 1 Pages: 183-190

    • DOI

      10.1016/j.jgr.2020.09.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MicroRNA-21 facilitates osteoblast activity2020

    • Author(s)
      Oka S, Li X, Zhang F, Tewari N, Ma R, Zhong L, Makishima M, Liu Y, Bhawal UK
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 25 Pages: 100894-100894

    • DOI

      10.1016/j.bbrep.2020.100894

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral toxicity to high level sodium fluoride causes impairment of autophagy2020

    • Author(s)
      Oka S, Li X, Zhang F, Taguchi C, Tewari N, Kim IS, Zhong L, Arikawa K, Liu Y, Bhawal UK
    • Journal Title

      Journal of Physiology and Pharmacology

      Volume: 71(5) Pages: 749-760

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dec1 deficiency protects the heart from fibrosis, inflammation, and myocardial cell apoptosis in a mouse model of cardiac hypertrophy.2020

    • Author(s)
      Li X, Le HT, Sato F, Kang TH, Makishima M, Zhong L, Liu Y, Guo L, Bhawal UK.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 532 Issue: 4 Pages: 513-519

    • DOI

      10.1016/j.bbrc.2020.08.058

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early effect of laser irradiation in signaling pathways of diabetic rat submandibular salivary glands2020

    • Author(s)
      Fukuoka CY, Vicari HP, Sipert CR, Bhawal UK, Abiko Y, Arana-Chavez VE, Simões A
    • Journal Title

      PLoS One

      Volume: 15(8) Issue: 8 Pages: e0236727-e0236727

    • DOI

      10.1371/journal.pone.0236727

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential role of DEC1 in cervical cancer cells involving overexpression and apoptosis2020

    • Author(s)
      Sato F, Bhawal UK, Sugiyama N, Osaki S, Oikawa K, Muragaki Y
    • Journal Title

      Clocks & Sleep

      Volume: 2(1) Issue: 1 Pages: 26-38

    • DOI

      10.3390/clockssleep2010004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of IL-17 for Monocyte Chemotactic Protein Production by Human Temporomandibular Joint Synovial Fibroblasts2019

    • Author(s)
      Bhawal UK, Li X, Wang C, Suzuki M, Oka S, Sato F, Okada H, Hiratsuka K
    • Journal Title

      International Journal of Oral-Medical Sciences

      Volume: 18 Issue: 1 Pages: 1-9

    • DOI

      10.5466/ijoms.18.1

    • NAID

      130007672316

    • ISSN
      1347-9733, 2185-4254
    • Year and Date
      2019-06-24
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Treatment with low‐level sodium fluoride on wound healing and the osteogenic differentiation of bone marrow mesenchymal stem cells2019

    • Author(s)
      Bhawal Ujjal K., Li Xiaoyan, Suzuki Masatoshi, Taguchi Chieko, Oka Shunichi, Arikawa Kazumune, Tewari Nitesh, Liu Yi
    • Journal Title

      Dental Traumatology

      Volume: ー Issue: 3 Pages: 1-1

    • DOI

      10.1111/edt.12532

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of 830 nm low-power laser irradiation on body weight gain and inflammatory cytokines in experimental diabetes in different animal models2019

    • Author(s)
      Bhawal UK, Yoshida K, Kurita T, Suzuki M, Okada Y, Tewari N, Oka S, Kuboyama N, Hiratsuka K
    • Journal Title

      LASER THERAPY

      Volume: 28 Issue: 4 Pages: 257-265

    • DOI

      10.5978/islsm.19-OR-17

    • NAID

      130007794756

    • ISSN
      0898-5901, 1884-7269
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dec1 deficiency suppresses cardiac perivascular fibrosis induced by transverse aortic constriction2019

    • Author(s)
      Le HT, Sato F, Kohsaka A, Bhawal UK, Nakao T, Muragaki Y, Nakata M
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20(19) Issue: 19 Pages: 4967-4967

    • DOI

      10.3390/ijms20194967

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Smad3 Suppresses Epithelial Cell Migration and Proliferation via the Clock Gene Dec1, Which Negatively Regulates the Expression of Clock Genes Dec2 and Per12019

    • Author(s)
      Fuyuki Sato, Tsuyoshi Otsuka, Akira Kohsaka, Hue Thi Le, Ujjal K. Bhawal, Yasuteru Muragaki
    • Journal Title

      American Journal of Pathology

      Volume: 189(4) Issue: 4 Pages: 773-783

    • DOI

      10.1016/j.ajpath.2019.01.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transcription factor DEC1 is required for maximal experimentally induced periodontal inflammation2018

    • Author(s)
      Zhang F, Suzuki M, Kim IS, Kobayashi R, Hamada N, Sato F, Bhawal UK
    • Journal Title

      Journal of Periodontal Research

      Volume: 53(5) Issue: 5 Pages: 883-893

    • DOI

      10.1111/jre.12578

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 徐放性低濃度フッ化物による創傷治癒の分子機構に関する研究2020

    • Author(s)
      木本 一成, バワール ウジャール, 前田 真史, 小田部 岳雄, 古澤 利武, 渡辺 孝夫
    • Organizer
      第50回日本口腔インプラント学会記念学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effect of low-level fluoride on wound healing and proliferation of bone marrow mesenchymal stem cells: critical insights2019

    • Author(s)
      Ujial K Bhawal
    • Organizer
      2nd National Conference of Indian Society for Dental Traumatology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Basic helix-loop-helix transcription factors DEC1 and DEC2 modulates P. gingivalis-induced inflammation2019

    • Author(s)
      Ujial K Bhawal
    • Organizer
      Hangzhou Normal University, Hangzhou, China
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Differentiated embryonic chondrocyte gene 1 (Dec1) deficiency inhibits TAC-induced fibrosis in cardiac hypertrophy2019

    • Author(s)
      Ujial K Bhawal, Hue Thi Le, Fuyuki Sato
    • Organizer
      The 2019 joint meeting of the American Society for Cell Biology (ASCB) and European Molecular Biology Organization (EMBO)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Role of basic helix-loop-helix transcription factor DEC2 in alveolar bone resorption2019

    • Author(s)
      Ujjal K Bhawal, Xiaoyan Li, Fengzhu Zhang, Masatoshi Suzuki, Lijia Guo, Yi Liu, Koh Shibutani
    • Organizer
      4th Meeting of the International Association for Dental Research Asia Pacific Region 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The regulatory role of micromolar level of sodium fluoride on osteoclastogenic differentiation2019

    • Author(s)
      Xiaoyan Li, Ujjal K Bhawal, Lijia Guo, Yi Liu, Koh Shibutani
    • Organizer
      4th Meeting of the International Association for Dental Research Asia Pacific Region 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular mechanism of basic helix-loop-helix transcription factor DEC2 in alveolar bone resorption2019

    • Author(s)
      Ujjal K Bhawal, Xiaoyan Li, Lijia Guo, Yi Liu
    • Organizer
      The 2019 Chinese National Annual Conference on Oral Biomedicine
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Smad3 suppresses epithelial cell migration and proliferation via the clock gene Dec12019

    • Author(s)
      Fuyuki Sato, Ujjal K Bhawal, Kosuke Oikawa, Yasuteru Muragaki
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 徐放性低濃度フッ化物による創傷治癒の分子機構に関する研究 - 骨芽細胞分化に関わるRunx2およびOsteocalcinの発現 -2019

    • Author(s)
      木本 一成,渡辺 孝夫,小田部 岳雄,村上 龍也,バワール ウジャール
    • Organizer
      第49回公益社団法人日本口腔インプラント学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] The regulatory role of microRNAs in the osteogenic differentiation of BMMSCs2019

    • Author(s)
      Xiaoyan Li, Ujjal K Bhawal, Lijia Guo, Yi Liu, Koh Shibutani
    • Organizer
      第19回口腔科学会 2019
    • Related Report
      2019 Research-status Report
  • [Presentation] Evaluation of bone morphology of Bio-Oss/HATCP/human allogenic bone scaffold transplantation in tooth extraction socket in mini pig2019

    • Author(s)
      Juan Du, Ujjal K Bhawal, Lijia Guo, Yi Liu, Koh Shibutani
    • Organizer
      第19回口腔科学会 2019
    • Related Report
      2019 Research-status Report
  • [Presentation] Low-Level Laser Therapy (LLLT): Drug free pain relief and better healing2019

    • Author(s)
      Ujjal K. Bhawal, Toshikazu Uchiyama, Fengzhu Zhang, Koh Shibutani
    • Organizer
      World Laser Medicine Congress 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] MicroRNA expression profiling and functional analysis of dysregulated microRNAs in bone aging2019

    • Author(s)
      Ujjal K Bhawal, Fengzhu Zhang, Kiyomi Yoshida, Makoto Makishima, Koh Shibutani, Koichi Hiratsuka
    • Organizer
      97th General Session & Exhibition of the IADR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Basic helix-loop-helix transcription factors DEC1 and DEC2 modulates P. gingivalis-induced inflammation2019

    • Author(s)
      Fengzhu Zhang, Ujjal K Bhawal, Masatoshi Suzuki, Michiharu Shimosaka, Koichi Hiratsuka, Koh Shibutani
    • Organizer
      97th General Session & Exhibition of the IADR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of low-level sodium fluoride in periodontal inflammation2019

    • Author(s)
      Chieko Taguchi, Toshikazu Uchiyama, Fengzhu Zhang, Ujjal K Bhawal, Kazumune Arikawa
    • Organizer
      97th General Session & Exhibition of the IADR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of mRNA-microRNA crosstalk in salivary glands aging through integrative transcriptome analysis2019

    • Author(s)
      Ujjal K. Bhawal, Fengzhu Zhang, Kiyomi Yoshida, Ikuo Nasu
    • Organizer
      一般社団法人日本老年歯科医学会第30回学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] SATB1遺伝子欠損マウスにおけるシェーグレン症候群発症機構の解析2019

    • Author(s)
      張 鳳洙、バワール ウジャール、那須郁夫
    • Organizer
      一般社団法人日本老年歯科医学会第30回学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Sjogren’s syndrome in SATB1 conditional knockout mice2019

    • Author(s)
      Ujjal K Bhawal, Fengzhu Zhang, Yuriko Tanaka, Yumi Ito, Motonari Kondo, Kazumune Arikawa, Koichi Hiratsuka
    • Organizer
      第68回日本口腔衛生学会・総会
    • Related Report
      2019 Research-status Report
  • [Presentation] TGF-β1 induced Connexin43 promotes scar formation2019

    • Author(s)
      Xiaoyan Li, Ujjal K Bhawal, Lijia Guo, Yi Liu
    • Organizer
      第68回日本口腔衛生学会・総会
    • Related Report
      2019 Research-status Report
  • [Presentation] The efficiency of Er:YAG laser in chronic periodontitis2019

    • Author(s)
      uan Du, Lijia Guo, Ujjal K Bhawal, Yi Liu
    • Organizer
      第68回日本口腔衛生学会・総会
    • Related Report
      2019 Research-status Report
  • [Presentation] The role of low-level sodium fluoride in periodontal inflammation2019

    • Author(s)
      Fengzhu Zhang, Ujjal K Bhawal, Koh Shibutani
    • Organizer
      第68回日本口腔衛生学会・総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 低出力レーザー照射によるSTZ誘発糖尿病ラットのAGE-RAGE系に及ぼす影響2019

    • Author(s)
      田口 千恵子、内山 敏一、張 鳳洙、バワール ウジャール、有川 量崇
    • Organizer
      第68回日本口腔衛生学会・総会
    • Related Report
      2019 Research-status Report
  • [Presentation] CXCL14のエピジェネティクス制御機構は口腔癌の病態生理に関与する2019

    • Author(s)
      Ujjal K Bhawal, Tomonori Sasahira, Fuyuki Sato, Hiroki Kuniyasu
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 子宮頸癌においてBHLH型転写因子DEC1発現は幹細胞マーカーSOX2とc-MYC発現を制御する2019

    • Author(s)
      杉山 奈生、佐藤 冬樹、尾崎 祥子、バワール ウジャール クマール、及川 恒輔、村垣 泰光
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 口腔癌の発育・進展に関わる時計遺伝子DEC1とCK1εの新たな機能とその意義2019

    • Author(s)
      尾崎 祥子、佐藤 冬樹、杉山 奈生、バワール ウジャール クマール、村田 晋一、村垣 泰光
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Knowledge, attitude, awareness and practice for prevention and emergency management of traumatic dental injuries school teachers in the world: global systematic review2018

    • Author(s)
      Ujjal K. Bhawal, Nitesh Tewari, Vijay P Mathur
    • Organizer
      第82回全国学校歯科保健研究大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Insights into the mechanisms of low-level fluoride: current status and future expectations2018

    • Author(s)
      Ujjal K. Bhawal, Yu Fujita, Ikuo Nasu, Hirohisa Arakawa
    • Organizer
      13th International Conference of the Asian Academy of Preventive Dentistry
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Insights into the mechanisms of low-level fluoride: current status and future expectations2018

    • Author(s)
      バワール ウジャール, 内山敏一, 有川量祟, 田口千恵子, 横田容子, 藤田(中島)光, 景山万貴子, 大峰浩隆, 平山聡司
    • Organizer
      ジャパンオーラルヘルス学会第21回学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Insights into the mechanisms of low-level fluoride: current status and future expectations2018

    • Author(s)
      Ujjal K. Bhawal
    • Organizer
      1st Indian Society of Dental Traumatology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Differentiated embryo chondrocyte 1 (DEC1) is a novel negative regulator of hepatic fibroblast growth factor 21 (FGF21) in aging mice2018

    • Author(s)
      Ujjal K. Bhawal, Makoto Makishima
    • Organizer
      2018 ICAD (3rd ICAD)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clock gene DEC1 regulates the expression of stem cell marker genes SOX2 and c-MYC in cervical cancer2018

    • Author(s)
      Fuyuki Sato, Ujjal Bhawal, Kosuke Oikawa, Yasuteru Muragaki
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] SATB1遺伝子欠損マウスにおけるシェーグレン症候群発症機構の解析2018

    • Author(s)
      田中ゆり子、バワール ウジャール、張 鳳洙、近藤元就
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 転写因子DEC1は実験的に誘導された歯周炎の制御に重要である2018

    • Author(s)
      バワール ウジャール、張 鳳洙、鈴木 正敏、藤田 裕、小林 良喜、平塚 浩一、渋谷 鑛
    • Organizer
      第18回口腔科学会 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] Low-Level Laser Therapy (LLLT): Drug free pain relief and better healing2018

    • Author(s)
      Ujjal K. Bhawal
    • Organizer
      第30回日本レーザー治療学会学術集会・総会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Role of stromal cell-derived factor 1 alpha and CXCR4 in Porphyromonas gingivalis-induced periodontal inflammation2018

    • Author(s)
      Fengzhu Zhang, Ujjal K. Bhawal, Chieko Taguchi, Kazumune Arikawa, Ikuo Nasu, Hirohisa Arakawa, Koh Shibutani
    • Organizer
      第67回日本口腔衛生学会・総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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