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  3. Delineating, Imaging, and Assessing Pulmonary Fibrosis Remodeling via Collagen Hybridization

Delineating, Imaging, and Assessing Pulmonary Fibrosis Remodeling via Collagen Hybridization

  • ACS Nano. 2024 Oct 15;18(41):27997-28011. doi: 10.1021/acsnano.4c06139.
Jie Zhao 1,  Wenjun Yu 1 2,  Daoning Zhou 1,  Yinghua Liu 1,  Jingyue Wei 1 3,  Lei Bi 1,  Suwen Zhao 1,  Jianzhong He 4,  Jing Liu 5,  Jin Su 6,  Hongjun Jin 1,  Ye Liu 4,  Hong Shan 1 7,  Man Li 1 3,  Yaqin Zhang 2,  Yang Li 1
Affiliations

Affiliations

  • 1 Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • 2 Department of Radiology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • 3 Biobank and Department of Information Technology and Data Center, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • 4 Department of Pathology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • 5 Department of Pulmonary and Critical Care Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • 6 State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China.
  • 7 Department of Interventional Medicine, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
PMID: 39361472 DOI: 10.1021/acsnano.4c06139
Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening disease with no early detection, few treatments, and dismal outcomes. Although collagen overdeposition is a hallmark of lung fibrosis, current research mostly focuses on the cellular aspect, leaving collagen, particularly its dynamic remodeling (i.e., degradation and turnover), largely unexplored. Here, using a collagen hybridizing peptide (CHP) that specifically binds unfolded collagen chains, we reveal vast collagen denaturation in human IPF lungs and delineate the spatiotemporal progression of collagen denaturation three-dimensionally within fibrotic lungs in mice. Transcriptomic analyses support that lung collagen denaturation is strongly associated with up-regulated collagen catabolism in mice and patients. We thus show that CHP probing differentiates remodeling responses to antifibrotics and highlights the resolution of established fibrosis by agents up-regulating collagen catabolism. We further develop a radioactive CHP that detects fibrosis in vivo in mice as early as 7 days postlung-injury (Ashcroft score: 2-3) by positron emission tomography (PET) imaging and ex vivo in clinical lung specimens. These findings establish collagen denaturation as a promising marker of fibrotic remodeling for the investigation, diagnosis, and therapeutic development of pulmonary fibrosis.

Keywords

collagen catabolism; extracellular matrix remodeling; light sheet fluorescence microscopy; positron emission tomography imaging; pulmonary fibrosis; therapeutic assessment; transcriptomic analysis.

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