2. Academic Validation
  3. PIEZO1 mediates periostin+ myofibroblast activation and pulmonary fibrosis in mice

PIEZO1 mediates periostin+ myofibroblast activation and pulmonary fibrosis in mice

  • J Clin Invest. 2025 Jun 2;135(11):e184158. doi: 10.1172/JCI184158.
Liran Xu 1,  Ting Li 1,  Yapeng Cao 1,  Yu He 1,  Zehua Shao 1,  Siyu Liu 1,  Bianbian Wang 2,  Ailing Su 3,  Huijing Tian 1,  Yongxin Li 1,  Guozheng Liang 4,  Changhe Wang 2,  John Shyy 5,  Ying Xiong 6,  Fangyuan Chen 6,  Jason Xj Yuan 7,  Junjun Liu 8,  Bin Zhou 9,  Nina Wettschureck 4,  Stefan Offermanns 4,  Yang Yan 1,  Zuyi Yuan 6,  Shengpeng Wang 4 6
Affiliations

Affiliations

  • 1 Department of Cardiac Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education.
  • 2 Center for Mitochondrial Biology and Medicine, School of Life Science and Technology, and.
  • 3 Biobank, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 4 Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  • 5 Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • 6 Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 7 The Herbert Wertheim UF Scripps Institute, University of Florida, Jupiter, Florida, USA.
  • 8 Shaanxi Techshake Biotechnology, Xi'an, Shaanxi, China.
  • 9 New Cornerstone Science Laboratory, State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
PMID: 40454481 DOI: 10.1172/JCI184158
Abstract

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by the excessive accumulation of activated myofibroblasts that deposit extracellular matrix (ECM) protein, leading to progressive scar formation and mechanical stress. However, the cellular origin and fate of myofibroblasts remain controversial, and the mechanisms by which myofibroblasts sense mechanical cues in the lung are unclear. Here, we report that periostin (Postn) is a reliable and distinctive marker for pulmonary myofibroblasts, while ablation of Postn+ myofibroblasts after injury ameliorated lung fibrosis. PIEZO1 was highly expressed in Postn+ myofibroblast and played a vital role in mechanoactivation of Postn+ myofibroblast and development of lung fibrosis. Conditional deletion of Piezo1 in Postn+ myofibroblasts significantly inhibited lung fibrosis by suppressing myofibroblast activation and proliferation. Loss of Piezo1 led to disruption of actin organization and prevention of YAP/Taz nuclear localization, thus shifting the myofibroblasts from a proliferative state into a stressed and apoptotic state. Furthermore, myofibroblast-specific YAP/Taz deletion fully recapitulated the protective phenotypes of myofibroblast-Piezo1-KO mice. These findings show that periostin marks pulmonary myofibroblasts, and that PIEZO1-mediated mechanosensation is essential for myofibroblast activation in the lung. Targeting PIEZO1 in the periostin-expressing cells is a novel therapeutic option to interfere with fibrotic diseases such as IPF .

Keywords

Cell biology; Fibrosis; Ion channels; Pulmonology.

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