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Staab-Weijnitz, C.A.

Fighting the fiber: Targeting collagen in lung fibrosis.

Am. J. Respir. Cell Mol. Biol. 66, 363-381 (2022)
Verlagsversion Postprint DOI PMC
Open Access Green
Organ fibrosis is characterized by epithelial injury and aberrant tissue repair, where activated effector cells, mostly fibroblasts and myofibroblasts, excessively deposit collagen into the extracellular matrix. Fibrosis frequently results in organ failure and has been estimated to contribute to at least one third of all global deaths. Also lung fibrosis, in particular idiopathic pulmonary fibrosis (IPF), is a fatal disease with rising incidence worldwide. As current treatment options targeting fibrogenesis are insufficient, there is an urgent need for novel therapeutic strategies. During the last decade, several studies have proposed to target intra- and extracellular components of the collagen biosynthesis, maturation, and degradation machinery. This includes intra- and extracellular targets directly acting on collagen gene products, but also such that anabolize essential building blocks of collagen, in particular glycine and proline biosynthetic enzymes. Collagen, however, is a ubiquitous molecule in the body and fulfils essential functions as a macromolecular scaffold, growth factor reservoir, and receptor binding site in virtually every tissue. This review summarizes recent advances and future directions in this field. Evidence for the proposed therapeutic targets and where they currently stand in terms of clinical drug development for treatment of fibrotic disease is provided. The drug targets are furthermore discussed in light of (1) specificity for collagen biosynthesis, maturation and degradation, and (2) specificity for disease-associated collagen. As therapeutic success and safety of these drugs may largely depend on targeted delivery, different strategies for specific delivery to the main effector cells and to the extracellular matrix are discussed.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Fkbp10 ; Hsp47 ; Larp6 ; Lysyl Oxidase ; Prolyl Hydroxylase
ISSN (print) / ISBN 1044-1549
e-ISSN 1535-4989
Zeitschrift American Journal of Respiratory Cell and Molecular Biology
Quellenangaben Band: 66, Heft: 4, Seiten: 363-381 Artikelnummer: , Supplement: ,
Verlag American Thoracic Society
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Lung Health and Immunity (LHI)