IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35390-3.html
   My bibliography  Save this article

Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling

Author

Listed:
  • David E. Lee

    (Duke University School of Medicine
    Duke University School of Medicine)

  • Lauren K. McKay

    (Duke University School of Medicine
    University of North Carolina at Chapel Hill)

  • Akshay Bareja

    (Duke University School of Medicine
    Duke University School of Medicine)

  • Yongwu Li

    (Duke University)

  • Alastair Khodabukus

    (Duke University)

  • Nenad Bursac

    (Duke University)

  • Gregory A. Taylor

    (VA Health Care System
    Duke University School of Medicine
    Duke University School of Medicine
    Duke University School of Medicine)

  • Gurpreet S. Baht

    (Duke University School of Medicine
    Duke University School of Medicine)

  • James P. White

    (Duke University School of Medicine
    Duke University School of Medicine
    Duke University School of Medicine)

Abstract

Pathologies associated with sarcopenia include decline in muscular strength, lean mass and regenerative capacity. Despite the substantial impact on quality of life, no pharmacological therapeutics are available to counteract the age-associated decline in functional capacity and/or, resilience. Evidence suggests immune-secreted cytokines can improve muscle regeneration, a strategy which we leverage in this study by rescuing the age-related deficiency in Meteorin-like through several in vivo add-back models. Notably, the intramuscular, peptide injection of recombinant METRNL was sufficient to improve muscle regeneration in aging. Using ex vivo media exchange and in vivo TNF inhibition, we demonstrate a mechanism of METRNL action during regeneration, showing it counteracts a pro-fibrotic gene program by triggering TNFα-induced apoptosis of fibro/adipogenic progenitor cells. These findings demonstrate therapeutic applications for METRNL to improve aged muscle, and show Fibro/Adipogenic Progenitors are viable therapeutic targets to counteract age-related loss in muscle resilience.

Suggested Citation

  • David E. Lee & Lauren K. McKay & Akshay Bareja & Yongwu Li & Alastair Khodabukus & Nenad Bursac & Gregory A. Taylor & Gurpreet S. Baht & James P. White, 2022. "Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35390-3
    DOI: 10.1038/s41467-022-35390-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35390-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-35390-3?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. Gurpreet S. Baht & David Silkstone & Linda Vi & Puviindran Nadesan & Yasha Amani & Heather Whetstone & Qingxia Wei & Benjamin A. Alman, 2015. "Exposure to a youthful circulation rejuvenates bone repair through modulation of β-catenin," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    2. Min Shang & Federica Cappellesso & Ricardo Amorim & Jens Serneels & Federico Virga & Guy Eelen & Stefania Carobbio & Melvin Y. Rincon & Pierre Maechler & Katrien Bock & Ping-Chih Ho & Marco Sandri & B, 2020. "Macrophage-derived glutamine boosts satellite cells and muscle regeneration," Nature, Nature, vol. 587(7835), pages 626-631, November.
    3. Irina M. Conboy & Michael J. Conboy & Amy J. Wagers & Eric R. Girma & Irving L. Weissman & Thomas A. Rando, 2005. "Rejuvenation of aged progenitor cells by exposure to a young systemic environment," Nature, Nature, vol. 433(7027), pages 760-764, February.
    4. Suoqin Jin & Christian F. Guerrero-Juarez & Lihua Zhang & Ivan Chang & Raul Ramos & Chen-Hsiang Kuan & Peggy Myung & Maksim V. Plikus & Qing Nie, 2021. "Inference and analysis of cell-cell communication using CellChat," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    5. Hongqing Du & Chung-Hsuan Shih & Michael N. Wosczyna & Alisa A. Mueller & Joonseok Cho & Abhishek Aggarwal & Thomas A. Rando & Brian J. Feldman, 2017. "Macrophage-released ADAMTS1 promotes muscle stem cell activation," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    6. Gurpreet S. Baht & David Silkstone & Linda Vi & Puviindran Nadesan & Yasha Amani & Heather Whetstone & Qingxia Wei & Benjamin A. Alman, 2015. "Erratum: Exposure to a youthful circulation rejuvenates bone repair through modulation of β-catenin," Nature Communications, Nature, vol. 6(1), pages 1-1, November.
    7. Joe V. Chakkalakal & Kieran M. Jones & M. Albert Basson & Andrew S. Brack, 2012. "The aged niche disrupts muscle stem cell quiescence," Nature, Nature, vol. 490(7420), pages 355-360, October.
    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. Felicia Lazure & Rick Farouni & Korin Sahinyan & Darren M. Blackburn & Aldo Hernández-Corchado & Gabrielle Perron & Tianyuan Lu & Adrien Osakwe & Jiannis Ragoussis & Colin Crist & Theodore J. Perkins , 2023. "Transcriptional reprogramming of skeletal muscle stem cells by the niche environment," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    3. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Qingnan Liang & Yuefan Huang & Shan He & Ken Chen, 2023. "Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    6. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Moujtaba Y. Kasmani & Paytsar Topchyan & Ashley K. Brown & Ryan J. Brown & Xiaopeng Wu & Yao Chen & Achia Khatun & Donia Alson & Yue Wu & Robert Burns & Chien-Wei Lin & Matthew R. Kudek & Jie Sun & We, 2023. "A spatial sequencing atlas of age-induced changes in the lung during influenza infection," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Wei Yang & Li-Bo Liu & Feng-Liang Liu & Yan-Hua Wu & Zi-Da Zhen & Dong-Ying Fan & Zi-Yang Sheng & Zheng-Ran Song & Jia-Tong Chang & Yong-Tang Zheng & Jing An & Pei-Gang Wang, 2023. "Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    9. Luke Simpson & Andrew Strange & Doris Klisch & Sophie Kraunsoe & Takuya Azami & Daniel Goszczynski & Triet Minh & Benjamin Planells & Nadine Holmes & Fei Sang & Sonal Henson & Matthew Loose & Jennifer, 2024. "A single-cell atlas of pig gastrulation as a resource for comparative embryology," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. Jeffrey C. Gerrard & Jamison P. Hay & Ryan N. Adams & James C. Williams & Joshua R. Huot & Kaitlin M. Weathers & Joseph S. Marino & Susan T. Arthur, 2021. "Current Thoughts of Notch’s Role in Myoblast Regulation and Muscle-Associated Disease," IJERPH, MDPI, vol. 18(23), pages 1-20, November.
    11. Xiaojian Lu & Yanwei Luo & Xichen Nie & Bailing Zhang & Xiaoyan Wang & Ran Li & Guangmin Liu & Qianyin Zhou & Zhizhong Liu & Liqing Fan & James M. Hotaling & Zhe Zhang & Hao Bo & Jingtao Guo, 2023. "Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Xiaoyan Wei & Angelos Rigopoulos & Matthias Lienhard & Sophie Pöhle-Kronawitter & Georgios Kotsaris & Julia Franke & Nikolaus Berndt & Joy Orezimena Mejedo & Hao Wu & Stefan Börno & Bernd Timmermann &, 2024. "Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    13. Anjun Ma & Xiaoying Wang & Jingxian Li & Cankun Wang & Tong Xiao & Yuntao Liu & Hao Cheng & Juexin Wang & Yang Li & Yuzhou Chang & Jinpu Li & Duolin Wang & Yuexu Jiang & Li Su & Gang Xin & Shaopeng Gu, 2023. "Single-cell biological network inference using a heterogeneous graph transformer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    14. Jeff DeMartino & Michael T. Meister & Lindy L. Visser & Mariël Brok & Marian J. A. Groot Koerkamp & Amber K. L. Wezenaar & Laura S. Hiemcke-Jiwa & Terezinha Souza & Johannes H. M. Merks & Anne C. Rios, 2023. "Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    15. Zi-Xun Yan & Yan Dong & Niu Qiao & Yi-Lun Zhang & Wen Wu & Yue Zhu & Li Wang & Shu Cheng & Peng-Peng Xu & Zi-Song Zhou & Ling-Shuang Sheng & Wei-Li Zhao, 2024. "Cholesterol efflux from C1QB-expressing macrophages is associated with resistance to chimeric antigen receptor T cell therapy in primary refractory diffuse large B cell lymphoma," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Junjun Jing & Jifan Feng & Yuan Yuan & Tingwei Guo & Jie Lei & Fei Pei & Thach-Vu Ho & Yang Chai, 2022. "Spatiotemporal single-cell regulatory atlas reveals neural crest lineage diversification and cellular function during tooth morphogenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    17. Daniel Dimitrov & Dénes Türei & Martin Garrido-Rodriguez & Paul L. Burmedi & James S. Nagai & Charlotte Boys & Ricardo O. Ramirez Flores & Hyojin Kim & Bence Szalai & Ivan G. Costa & Alberto Valdeoliv, 2022. "Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    18. Xi Li & Alfonso Poire & Kang Jin Jeong & Dong Zhang & Tugba Yildiran Ozmen & Gang Chen & Chaoyang Sun & Gordon B. Mills, 2024. "C5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    19. Nunya Chotiwan & Ebba Rosendal & Stefanie M. A. Willekens & Erin Schexnaydre & Emma Nilsson & Richard Lindqvist & Max Hahn & Ionut Sebastian Mihai & Federico Morini & Jianguo Zhang & Gregory D. Ebel &, 2023. "Type I interferon shapes brain distribution and tropism of tick-borne flavivirus," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    20. Vishnu Muraleedharan Saraswathy & Lili Zhou & Mayssa H. Mokalled, 2024. "Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair," Nature Communications, Nature, vol. 15(1), pages 1-21, 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:13:y:2022:i:1:d:10.1038_s41467-022-35390-3. 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.