IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37043-5.html
   My bibliography  Save this article

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice

Author

Listed:
  • Yunwen Yang

    (Children’s Hospital of Nanjing Medical University
    Children’s Hospital of Nanjing Medical University
    Nanjing Medical University)

  • Suwen Liu

    (Shandong Provincial Hospital Affiliated to Shandong First Medical University)

  • Peipei Wang

    (Children’s Hospital of Nanjing Medical University
    Children’s Hospital of Nanjing Medical University
    Nanjing Medical University)

  • Jing Ouyang

    (Children’s Hospital of Nanjing Medical University
    Children’s Hospital of Nanjing Medical University
    Nanjing Medical University)

  • Ning Zhou

    (Children’s Hospital of Nanjing Medical University
    Children’s Hospital of Nanjing Medical University
    Nanjing Medical University)

  • Yue Zhang

    (Children’s Hospital of Nanjing Medical University
    Children’s Hospital of Nanjing Medical University
    Nanjing Medical University)

  • Songming Huang

    (Children’s Hospital of Nanjing Medical University
    Children’s Hospital of Nanjing Medical University
    Nanjing Medical University)

  • Zhanjun Jia

    (Children’s Hospital of Nanjing Medical University
    Children’s Hospital of Nanjing Medical University
    Nanjing Medical University)

  • Aihua Zhang

    (Children’s Hospital of Nanjing Medical University
    Children’s Hospital of Nanjing Medical University
    Nanjing Medical University)

Abstract

Kidney injury initiates epithelial dedifferentiation and myofibroblast activation during the progression of chronic kidney disease. Herein, we find that the expression of DNA-PKcs is significantly increased in the kidney tissues of both chronic kidney disease patients and male mice induced by unilateral ureteral obstruction and unilateral ischemia-reperfusion injury. In vivo, knockout of DNA-PKcs or treatment with its specific inhibitor NU7441 hampers the development of chronic kidney disease in male mice. In vitro, DNA-PKcs deficiency preserves epithelial cell phenotype and inhibits fibroblast activation induced by transforming growth factor-beta 1. Additionally, our results show that TAF7, as a possible substrate of DNA-PKcs, enhances mTORC1 activation by upregulating RAPTOR expression, which subsequently promotes metabolic reprogramming in injured epithelial cells and myofibroblasts. Taken together, DNA-PKcs can be inhibited to correct metabolic reprogramming via the TAF7/mTORC1 signaling in chronic kidney disease, and serve as a potential target for treating chronic kidney disease.

Suggested Citation

  • Yunwen Yang & Suwen Liu & Peipei Wang & Jing Ouyang & Ning Zhou & Yue Zhang & Songming Huang & Zhanjun Jia & Aihua Zhang, 2023. "DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37043-5
    DOI: 10.1038/s41467-023-37043-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37043-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-37043-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Mei T. Tran & Zsuzsanna K. Zsengeller & Anders H. Berg & Eliyahu V. Khankin & Manoj K. Bhasin & Wondong Kim & Clary B. Clish & Isaac E. Stillman & S. Ananth Karumanchi & Eugene P. Rhee & Samir M. Pari, 2016. "PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection," Nature, Nature, vol. 531(7595), pages 528-532, March.
    2. Hui Peng & Qianqian Wang & Tanqi Lou & Jun Qin & Sungyun Jung & Vivekananda Shetty & Feng Li & Yanlin Wang & Xin-hua Feng & William E. Mitch & Brett H. Graham & Zhaoyong Hu, 2017. "Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Markus M. Rinschen & Oleg Palygin & Ashraf El-Meanawy & Xavier Domingo-Almenara & Amelia Palermo & Lashodya V. Dissanayake & Daria Golosova & Michael A. Schafroth & Carlos Guijas & Fatih Demir & Johan, 2022. "Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Koki Mise & Jianyin Long & Daniel L. Galvan & Zengchun Ye & Guizhen Fan & Rajesh Sharma & Irina I. Serysheva & Travis I. Moore & Collene R. Jeter & M. Anna Zal & Motoo Araki & Jun Wada & Paul T. Schum, 2024. "NDUFS4 regulates cristae remodeling in diabetic kidney disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37043-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.