IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51736-5.html
   My bibliography  Save this article

Lipid synthesis, triggered by PPARγ T166 dephosphorylation, sustains reparative function of macrophages during tissue repair

Author

Listed:
  • Shiman Zuo

    (Nanjing University)

  • Yuxin Wang

    (Nanjing University)

  • Hanjing Bao

    (Nanjing University)

  • Zehui Zhang

    (Nanjing University)

  • Nanfei Yang

    (Nanjing University)

  • Meng Jia

    (Nanjing University)

  • Qing Zhang

    (Nanjing University)

  • Ani Jian

    (Nanjing University)

  • Rong Ji

    (Nanjing University)

  • Lidan Zhang

    (Nanjing University)

  • Yan Lu

    (Nanjing University)

  • Yahong Huang

    (Nanjing University)

  • Pingping Shen

    (Nanjing University
    Shenzhen Research Institute of Nanjing University)

Abstract

Macrophages may acquire a reparative phenotype that supports tissue repair and remodeling in response to tissue injury. However, the metabolic requirements underpinning this process are incompletely understood. Here, we show that posttranslational modification (PTM) of PPARγ regulates lipid synthesis in response to wound microenvironmental cues and that metabolic rewiring orchestrates function of reparative macrophages. In injured tissues, repair signaling leads to decreased macrophage PPARγ threonine 166 (T166) phosphorylation, which results in a partially active PPARγ transcriptional program comprised of increased binding activity to the regulator regions of lipid synthesis-associated genes, thereby increased lipogenesis. The accumulated lipids serve as signaling molecules, triggering STAT3-mediated growth factor expression, and supporting the synthesis of phospholipids for the expansion of the endoplasmic reticulum (ER), which is required for protein secretion. Genetic or pharmacological inhibition of PPARγ T166 phosphorylation promotes the reparative function of macrophages and facilitates tissue regeneration. In summary, our work identifies PPARγ T166-regulated lipid biosynthesis as an essential pathway for meeting the anabolic demands of the activation and function of macrophages and provides a rationale for potential therapeutic targeting of tissue repair.

Suggested Citation

  • Shiman Zuo & Yuxin Wang & Hanjing Bao & Zehui Zhang & Nanfei Yang & Meng Jia & Qing Zhang & Ani Jian & Rong Ji & Lidan Zhang & Yan Lu & Yahong Huang & Pingping Shen, 2024. "Lipid synthesis, triggered by PPARγ T166 dephosphorylation, sustains reparative function of macrophages during tissue repair," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51736-5
    DOI: 10.1038/s41467-024-51736-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51736-5
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51736-5?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. Mingming Zhang & Lixing Zhou & Yuejie Xu & Min Yang & Yilai Xu & Garrison Paul Komaniecki & Tatsiana Kosciuk & Xiao Chen & Xuan Lu & Xiaoping Zou & Maurine E. Linder & Hening Lin, 2020. "A STAT3 palmitoylation cycle promotes TH17 differentiation and colitis," Nature, Nature, vol. 586(7829), pages 434-439, October.
    2. George C. Linderman & Jun Zhao & Manolis Roulis & Piotr Bielecki & Richard A. Flavell & Boaz Nadler & Yuval Kluger, 2022. "Zero-preserving imputation of single-cell RNA-seq data," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. G. M. Tannahill & A. M. Curtis & J. Adamik & E. M. Palsson-McDermott & A. F. McGettrick & G. Goel & C. Frezza & N. J. Bernard & B. Kelly & N. H. Foley & L. Zheng & A. Gardet & Z. Tong & S. S. Jany & S, 2013. "Succinate is an inflammatory signal that induces IL-1β through HIF-1α," Nature, Nature, vol. 496(7444), pages 238-242, April.
    4. Thomas A. Wynn & Ajay Chawla & Jeffrey W. Pollard, 2013. "Macrophage biology in development, homeostasis and disease," Nature, Nature, vol. 496(7446), pages 445-455, April.
    5. Geoffrey C. Gurtner & Sabine Werner & Yann Barrandon & Michael T. Longaker, 2008. "Wound repair and regeneration," Nature, Nature, vol. 453(7193), pages 314-321, May.
    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. Yichuan Cao & Xiamiao Zhao & Songming Tang & Qun Jiang & Sijie Li & Siyu Li & Shengquan Chen, 2024. "scButterfly: a versatile single-cell cross-modality translation method via dual-aligned variational autoencoders," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Li Yang & Dan Zhang & Wenjing Li & Hongbing Lin & Chendi Ding & Qingyun Liu & Liangliang Wang & Zimu Li & Lin Mei & Hongzhong Chen & Yanli Zhao & Xiaowei Zeng, 2023. "Biofilm microenvironment triggered self-enhancing photodynamic immunomodulatory microneedle for diabetic wound therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Hao Chen & Frederick J. King & Bin Zhou & Yu Wang & Carter J. Canedy & Joel Hayashi & Yang Zhong & Max W. Chang & Lars Pache & Julian L. Wong & Yong Jia & John Joslin & Tao Jiang & Christopher Benner , 2024. "Drug target prediction through deep learning functional representation of gene signatures," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Du Wenqiang & Ashkan Novin & Yamin Liu & Junaid Afzal & Yasir Suhail & Shaofei Liu & Nicole R. Gavin & Jennifer R. Jorgensen & Christopher M. Morosky & Reinaldo Figueroa & Tannin A. Schmidt & Melinda , 2024. "Scar matrix drives Piezo1 mediated stromal inflammation leading to placenta accreta spectrum," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Shiri Kuperman & Ram Efraty & Ina Arie & Arkadi Rahmanov & Marina Rahmanov Gavrielov & Matityahau Noff & Ron Fishel & Sandu Pitaru, 2020. "Examination of the Therapeutic Potential of Mouse Oral Mucosa Stem Cells in a Wound-Healing Diabetic Mice Model," IJERPH, MDPI, vol. 17(13), pages 1-10, July.
    6. Heewon Cho & Haw-Young Kwon & Amit Sharma & Sun Hyeok Lee & Xiao Liu & Naoki Miyamoto & Jong-Jin Kim & Sin-Hyeog Im & Nam-Young Kang & Young-Tae Chang, 2022. "Visualizing inflammation with an M1 macrophage selective probe via GLUT1 as the gating target," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    7. Zhenchao Tang & Guanxing Chen & Shouzhi Chen & Jianhua Yao & Linlin You & Calvin Yu-Chian Chen, 2024. "Modal-nexus auto-encoder for multi-modality cellular data integration and imputation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Hai Ni & Yinuo Wang & Kai Yao & Ling Wang & Jiancheng Huang & Yongfang Xiao & Hongyao Chen & Bo Liu & Cliff Y. Yang & Jijun Zhao, 2024. "Cyclical palmitoylation regulates TLR9 signalling and systemic autoimmunity in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Lu Jia & Yiyang Jiang & Lili Wu & Jingfei Fu & Juan Du & Zhenhua Luo & Lijia Guo & Junji Xu & Yi Liu, 2024. "Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    10. Sayan Chakraborty & Divyaleka Sampath & Melissa Ong Yu Lin & Matthew Bilton & Cheng-Kuang Huang & Mui Hoon Nai & Kizito Njah & Pierre-Alexis Goy & Cheng-Chun Wang & Ernesto Guccione & Chwee-Teck Lim &, 2021. "Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    11. Chen Chen & Bongsoo Park & Emeline Ragonnaud & Monica Bodogai & Xin Wang & Le Zong & Jung-Min Lee & Isabel Beerman & Arya Biragyn, 2022. "Cancer co-opts differentiation of B-cell precursors into macrophage-like cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Xiaowei Gu & Anna Heinrich & Shu-Yun Li & Tony DeFalco, 2023. "Testicular macrophages are recruited during a narrow fetal time window and promote organ-specific developmental functions," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. Chantal A. Ten Kate & Hilde J. H. Koese & M. Jenda Hop & André B. Rietman & René M. H. Wijnen & Marijn J. Vermeulen & Claudia M. G. Keyzer-Dekker, 2023. "Psychometric Performance of the Stony Brook Scar Evaluation Scale and SCAR-Q Questionnaire in Dutch Children after Pediatric Surgery," IJERPH, MDPI, vol. 21(1), pages 1-12, December.
    14. Kai Cheng & Bo Liu & Xiao-Shuai Zhang & Ruo-Yun Zhang & Fang Zhang & Ghazal Ashraf & Guo-Qing Fan & Ming-Yu Tian & Xing Sun & Jing Yuan & Yuan-Di Zhao, 2022. "Biomimetic material degradation for synergistic enhanced therapy by regulating endogenous energy metabolism imaging under hypothermia," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    15. Ishier Raote & Ann-Helen Rosendahl & Hanna-Maria Häkkinen & Carina Vibe & Ismail Küçükaylak & Mugdha Sawant & Lena Keufgens & Pia Frommelt & Kai Halwas & Katrina Broadbent & Marina Cunquero & Gustavo , 2024. "TANGO1 inhibitors reduce collagen secretion and limit tissue scarring," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    16. Ariel C. Vonk & Xiaofan Zhao & Zheyu Pan & Megan L. Hudnall & Conrad G. Oakes & Gabriela A. Lopez & Sarah C. Hasel-Kolossa & Alexander W. C. Kuncz & Sasha B. Sengelmann & Darian J. Gamble & Thomas P. , 2023. "Single-cell analysis of lizard blastema fibroblasts reveals phagocyte-dependent activation of Hedgehog-responsive chondrogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    17. Dorota Zawada & Jessica Kornherr & Anna B. Meier & Gianluca Santamaria & Tatjana Dorn & Monika Nowak-Imialek & Daniel Ortmann & Fangfang Zhang & Mark Lachmann & Martina Dreßen & Mariaestela Ortiz & Vi, 2023. "Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    18. Diana Boraschi & Dongjie Li & Yang Li & Paola Italiani, 2021. "In Vitro and In Vivo Models to Assess the Immune-Related Effects of Nanomaterials," IJERPH, MDPI, vol. 18(22), pages 1-16, November.
    19. Julian C. Bahr & Xiao-Yan Li & Tamar Y. Feinberg & Long Jiang & Stephen J. Weiss, 2022. "Divergent regulation of basement membrane trafficking by human macrophages and cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    20. Wen-Lan Yang & Weinan Qiu & Ting Zhang & Kai Xu & Zi-Juan Gu & Yu Zhou & Heng-Ji Xu & Zhong-Zhou Yang & Bin Shen & Yong-Liang Zhao & Qi Zhou & Ying Yang & Wei Li & Peng-Yuan Yang & Yun-Gui Yang, 2023. "Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis," Nature Communications, Nature, vol. 14(1), pages 1-16, 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:15:y:2024:i:1:d:10.1038_s41467-024-51736-5. 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.