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Fibrosis: from mechanisms to medicines

Author

Listed:
  • Neil C. Henderson

    (University of Edinburgh Centre for Inflammation Research, The Queen’s Medical Research Institute, Edinburgh BioQuarter
    University of Edinburgh)

  • Florian Rieder

    (Lerner Research Institute, Cleveland Clinic Foundation
    Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation)

  • Thomas A. Wynn

    (Inflammation & Immunology Research Unit, Pfizer Worldwide Research, Development & Medical)

Abstract

Fibrosis can affect any organ and is responsible for up to 45% of all deaths in the industrialized world. It has long been thought to be relentlessly progressive and irreversible, but both preclinical models and clinical trials in various organ systems have shown that fibrosis is a highly dynamic process. This has clear implications for therapeutic interventions that are designed to capitalize on this inherent plasticity. However, despite substantial progress in our understanding of the pathobiology of fibrosis, a translational gap remains between the identification of putative antifibrotic targets and conversion of this knowledge into effective treatments in humans. Here we discuss the transformative experimental strategies that are being leveraged to dissect the key cellular and molecular mechanisms that regulate fibrosis, and the translational approaches that are enabling the emergence of precision medicine-based therapies for patients with fibrosis.

Suggested Citation

  • Neil C. Henderson & Florian Rieder & Thomas A. Wynn, 2020. "Fibrosis: from mechanisms to medicines," Nature, Nature, vol. 587(7835), pages 555-566, November.
    • Handle: RePEc:nat:nature:v:587:y:2020:i:7835:d:10.1038_s41586-020-2938-9
    DOI: 10.1038/s41586-020-2938-9
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    Cited by:

    1. Yi Wang & Yuanhang Xu & Weijie Zhai & Zhinan Zhang & Yuhong Liu & Shujie Cheng & Hongyu Zhang, 2022. "In-situ growth of robust superlubricated nano-skin on electrospun nanofibers for post-operative adhesion prevention," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Toshiyuki Ko & Seitaro Nomura & Shintaro Yamada & Kanna Fujita & Takanori Fujita & Masahiro Satoh & Chio Oka & Manami Katoh & Masamichi Ito & Mikako Katagiri & Tatsuro Sassa & Bo Zhang & Satoshi Hatsu, 2022. "Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Huimei Chen & Gabriel Chew & Nithya Devapragash & Jui Zhi Loh & Kevin Y. Huang & Jing Guo & Shiyang Liu & Elisabeth Li Sa Tan & Shuang Chen & Nicole Gui Zhen Tee & Masum M. Mia & Manvendra K. Singh & , 2022. "The E3 ubiquitin ligase WWP2 regulates pro-fibrogenic monocyte infiltration and activity in heart fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    4. Yasufumi Katanasaka & Harumi Yabe & Noriyuki Murata & Minori Sobukawa & Yuga Sugiyama & Hikaru Sato & Hiroki Honda & Yoichi Sunagawa & Masafumi Funamoto & Satoshi Shimizu & Kana Shimizu & Toshihide Ha, 2024. "Fibroblast-specific PRMT5 deficiency suppresses cardiac fibrosis and left ventricular dysfunction in male mice," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Camille Cohen & Rana Mhaidly & Hugo Croizer & Yann Kieffer & Renaud Leclere & Anne Vincent-Salomon & Catherine Robley & Dany Anglicheau & Marion Rabant & Aurélie Sannier & Marc-Olivier Timsit & Sean E, 2024. "WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Zhuo-Ran Yang & Huinan Suo & Jing-Wen Fan & Niannian Lv & Kehan Du & Teng Ma & Huimin Qin & Yan Li & Liu Yang & Nuoya Zhou & Hao Jiang & Juan Tao & Jintao Zhu, 2024. "Endogenous stimuli-responsive separating microneedles to inhibit hypertrophic scar through remodeling the pathological microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Marie Bobowski-Gerard & Clémence Boulet & Francesco P. Zummo & Julie Dubois-Chevalier & Céline Gheeraert & Mohamed Bou Saleh & Jean-Marc Strub & Amaury Farce & Maheul Ploton & Loïc Guille & Jimmy Vand, 2022. "Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    8. Jiahao Gao & Ya Wang & Xianfu Meng & Xiaoshuang Wang & Fang Han & Hao Xing & Guanglei Lv & Li Zhang & Shiman Wu & Xingwu Jiang & Zhenwei Yao & Xiangming Fang & Jiawen Zhang & Wenbo Bu, 2024. "A FAPα-activated MRI nanoprobe for precise grading diagnosis of clinical liver fibrosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Di Liu & Yanling Song & Hui Chen & Yuchan You & Luwen Zhu & Jucong Zhang & Xinyi Xu & Jiahao Hu & Xiajie Huang & Xiaochuan Wu & Xiaoling Xu & Saiping Jiang & Yongzhong Du, 2023. "Anti-VEGFR2 F(ab′)2 drug conjugate promotes renal accumulation and glomerular repair in diabetic nephropathy," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Fabian Peisker & Maurice Halder & James Nagai & Susanne Ziegler & Nadine Kaesler & Konrad Hoeft & Ronghui Li & Eric M. J. Bindels & Christoph Kuppe & Julia Moellmann & Michael Lehrke & Christian Stopp, 2022. "Mapping the cardiac vascular niche in heart failure," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    11. Yuma Horii & Shoichi Matsuda & Chikashi Toyota & Takumi Morinaga & Takeo Nakaya & Soken Tsuchiya & Masaki Ohmuraya & Takanori Hironaka & Ryo Yoshiki & Kotaro Kasai & Yuto Yamauchi & Noburo Takizawa & , 2023. "VGLL3 is a mechanosensitive protein that promotes cardiac fibrosis through liquid–liquid phase separation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    12. Peng Wang & Zhitao Huang & Yili Peng & Hongwei Li & Tong Lin & Yingyu Zhao & Zheng Hu & Zhanmei Zhou & Weijie Zhou & Youhua Liu & Fan Fan Hou, 2022. "Circular RNA circBNC2 inhibits epithelial cell G2-M arrest to prevent fibrotic maladaptive repair," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    13. Satoya Yoshida & Tatsuya Yoshida & Kohei Inukai & Katsuhiro Kato & Yoshimitsu Yura & Tomoki Hattori & Atsushi Enomoto & Koji Ohashi & Takahiro Okumura & Noriyuki Ouchi & Haruya Kawase & Nina Wettschur, 2024. "Protein kinase N promotes cardiac fibrosis in heart failure by fibroblast-to-myofibroblast conversion," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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