Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The p21 dependent G2 arrest of the cell cycle in epithelial tubular cells links to the early stage of renal fibrosis

View ORCID ProfileTakayuki Koyano, Masumi Namba, Tomoe Kobayashi, Kyomi Nakakuni, Daisuke Nakano, Masaki Fukushima, Akira Nishiyama, Makoto Matsuyama
doi: https://doi.org/10.1101/560078
Takayuki Koyano
1Division of Molecular Genetics, Shigei Medical Research Institute, 2117 Yamada, Minami-ku, Okayama, 701-0202, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Takayuki Koyano
Masumi Namba
1Division of Molecular Genetics, Shigei Medical Research Institute, 2117 Yamada, Minami-ku, Okayama, 701-0202, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomoe Kobayashi
1Division of Molecular Genetics, Shigei Medical Research Institute, 2117 Yamada, Minami-ku, Okayama, 701-0202, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyomi Nakakuni
2Shigei Medical Research Hospital, 2117 Yamada, Minami-ku, Okayama, 701-0202, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daisuke Nakano
3Depertment of Pharmacology, Kagawa University Medical School, 1750-1 Ikenobe, Miki-cho, Kagawa, 761-0793, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masaki Fukushima
1Division of Molecular Genetics, Shigei Medical Research Institute, 2117 Yamada, Minami-ku, Okayama, 701-0202, Japan
2Shigei Medical Research Hospital, 2117 Yamada, Minami-ku, Okayama, 701-0202, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Akira Nishiyama
3Depertment of Pharmacology, Kagawa University Medical School, 1750-1 Ikenobe, Miki-cho, Kagawa, 761-0793, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Makoto Matsuyama
1Division of Molecular Genetics, Shigei Medical Research Institute, 2117 Yamada, Minami-ku, Okayama, 701-0202, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: matsuyama@shigei.or.jp
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Renal fibrosis is accompanied with the progression of chronic kidney disease (CKD). Despite a number of past and ongoing studies, our understanding of the underlying mechanisms remains elusive. Here we explored the progression of renal fibrosis by using a mouse model, unilateral ureter obstruction (UUO). We found that in the initial stage of the progression where extracellular matrix did not deposit yet, the proximal tubular cells arrested at the G2 of the cell cycle. This G2 arrest was induced prior to activation of both DNA damage checkpoint and Wnt/β-Catenin pathway. Further analyses in vivo and in vitro indicated the cyclin dependent kinase inhibitor p21 is involved in the G2 arrest after the damage. The newly produced monoclonal antibody against p21 revealed that the p21 levels were sharply upregulated in response to the damage during the initial stage, but dropped down toward the later stage. To examine the function of p21 in the progression of renal fibrosis, we constructed the novel p21 deficient mice by i-GONAD. Compared with wild-type mice, p21 deficient mice showed the exacerbation of the fibrosis. Thus we propose that during the initial stage of the fibrosis following the renal damage, tubular cells arrest in the G2 phase depending on p21, thereby safeguarding the kidney functions.

  • Abbreviations

    CDK
    cyclin dependent kinase
    UUO
    unilateral ureter obstruction
    ECM
    extracellular matrix
    i-GONAD
    improved-genome editing via oviductal nucleic acid delivery
    CKD
    chronic kidney disease
    AKI
    acute kidney injury
    DSB
    double strand break
    DDR
    DNA damage response
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
    Back to top
    PreviousNext
    Posted February 26, 2019.
    Download PDF
    Email

    Thank you for your interest in spreading the word about bioRxiv.

    NOTE: Your email address is requested solely to identify you as the sender of this article.

    Enter multiple addresses on separate lines or separate them with commas.
    The p21 dependent G2 arrest of the cell cycle in epithelial tubular cells links to the early stage of renal fibrosis
    (Your Name) has forwarded a page to you from bioRxiv
    (Your Name) thought you would like to see this page from the bioRxiv website.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Share
    The p21 dependent G2 arrest of the cell cycle in epithelial tubular cells links to the early stage of renal fibrosis
    Takayuki Koyano, Masumi Namba, Tomoe Kobayashi, Kyomi Nakakuni, Daisuke Nakano, Masaki Fukushima, Akira Nishiyama, Makoto Matsuyama
    bioRxiv 560078; doi: https://doi.org/10.1101/560078
    Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
    Citation Tools
    The p21 dependent G2 arrest of the cell cycle in epithelial tubular cells links to the early stage of renal fibrosis
    Takayuki Koyano, Masumi Namba, Tomoe Kobayashi, Kyomi Nakakuni, Daisuke Nakano, Masaki Fukushima, Akira Nishiyama, Makoto Matsuyama
    bioRxiv 560078; doi: https://doi.org/10.1101/560078

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Subject Area

    • Cell Biology
    Subject Areas
    All Articles
    • Animal Behavior and Cognition (3686)
    • Biochemistry (7766)
    • Bioengineering (5664)
    • Bioinformatics (21228)
    • Biophysics (10551)
    • Cancer Biology (8156)
    • Cell Biology (11901)
    • Clinical Trials (138)
    • Developmental Biology (6733)
    • Ecology (10387)
    • Epidemiology (2065)
    • Evolutionary Biology (13836)
    • Genetics (9691)
    • Genomics (13051)
    • Immunology (8119)
    • Microbiology (19929)
    • Molecular Biology (7823)
    • Neuroscience (42947)
    • Paleontology (318)
    • Pathology (1276)
    • Pharmacology and Toxicology (2256)
    • Physiology (3349)
    • Plant Biology (7207)
    • Scientific Communication and Education (1309)
    • Synthetic Biology (1998)
    • Systems Biology (5527)
    • Zoology (1126)