IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-021-27860-x.html
   My bibliography  Save this article

Lung emphysema and impaired macrophage elastase clearance in mucolipin 3 deficient mice

Author

Listed:
  • Barbara Spix

    (Ludwig-Maximilians-University)

  • Elisabeth S. Butz

    (Ludwig-Maximilians-University
    Institute for Neurophysiology, Hannover Medical School)

  • Cheng-Chang Chen

    (Ludwig-Maximilians-University
    National Taiwan University)

  • Anna Scotto Rosato

    (Ludwig-Maximilians-University)

  • Rachel Tang

    (Ludwig-Maximilians-University)

  • Aicha Jeridi

    (Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL))

  • Veronika Kudrina

    (Ludwig-Maximilians-University)

  • Eva Plesch

    (Ludwig-Maximilians-University)

  • Philipp Wartenberg

    (Saarland University, Center for Molecular Signaling (PZMS), Experimental Pharmacology)

  • Elisabeth Arlt

    (Ludwig-Maximilians-University)

  • Daria Briukhovetska

    (University Hospital Munich)

  • Meshal Ansari

    (Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL))

  • Gizem Günes Günsel

    (Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL))

  • Thomas M. Conlon

    (Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL))

  • Amanda Wyatt

    (Saarland University, Center for Molecular Signaling (PZMS), Experimental Pharmacology)

  • Sandra Wetzel

    (Christian-Albrechts-University Kiel)

  • Daniel Teupser

    (University Hospital Munich)

  • Lesca M. Holdt

    (University Hospital Munich)

  • Fabien Ectors

    (Liège University)

  • Ingrid Boekhoff

    (Ludwig-Maximilians-University)

  • Ulrich Boehm

    (Saarland University, Center for Molecular Signaling (PZMS), Experimental Pharmacology)

  • Jaime García-Añoveros

    (Northwestern University, Feinberg School of Medicine)

  • Paul Saftig

    (Christian-Albrechts-University Kiel)

  • Martin Giera

    (Leiden University Medical Center)

  • Sebastian Kobold

    (University Hospital Munich
    German Center for Translational Cancer Research (DKTK), partner site Munich)

  • Herbert B. Schiller

    (Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL))

  • Susanna Zierler

    (Ludwig-Maximilians-University
    Johannes-Keppler-University)

  • Thomas Gudermann

    (Ludwig-Maximilians-University
    German Center of Lung Research (DZL))

  • Christian Wahl-Schott

    (Institute for Neurophysiology, Hannover Medical School)

  • Franz Bracher

    (Ludwig-Maximilians-University)

  • Ali Önder Yildirim

    (Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL))

  • Martin Biel

    (Ludwig-Maximilians-University)

  • Christian Grimm

    (Ludwig-Maximilians-University)

Abstract

Lung emphysema and chronic bronchitis are the two most common causes of chronic obstructive pulmonary disease. Excess macrophage elastase MMP-12, which is predominantly secreted from alveolar macrophages, is known to mediate the development of lung injury and emphysema. Here, we discovered the endolysosomal cation channel mucolipin 3 (TRPML3) as a regulator of MMP-12 reuptake from broncho-alveolar fluid, driving in two independently generated Trpml3−/− mouse models enlarged lung injury, which is further exacerbated after elastase or tobacco smoke treatment. Mechanistically, using a Trpml3IRES-Cre/eR26-τGFP reporter mouse model, transcriptomics, and endolysosomal patch-clamp experiments, we show that in the lung TRPML3 is almost exclusively expressed in alveolar macrophages, where its loss leads to defects in early endosomal trafficking and endocytosis of MMP-12. Our findings suggest that TRPML3 represents a key regulator of MMP-12 clearance by alveolar macrophages and may serve as therapeutic target for emphysema and chronic obstructive pulmonary disease.

Suggested Citation

  • Barbara Spix & Elisabeth S. Butz & Cheng-Chang Chen & Anna Scotto Rosato & Rachel Tang & Aicha Jeridi & Veronika Kudrina & Eva Plesch & Philipp Wartenberg & Elisabeth Arlt & Daria Briukhovetska & Mesh, 2022. "Lung emphysema and impaired macrophage elastase clearance in mucolipin 3 deficient mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27860-x
    DOI: 10.1038/s41467-021-27860-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27860-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-27860-x?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Huirui Wang & Xiaona You & Jingcheng Wang & Xinyi Chen & Yinghui Gao & Mengmeng Wang & Wenru Zhang & Jiaozhen Zhang & Yang Yu & Bo Han & Mei Qi & Xiaohui Liu & Hongxiang Lou & Ting Dong, 2024. "MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis," Nature Communications, Nature, vol. 15(1), pages 1-17, 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_s41467-021-27860-x. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.