% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Bonatti:282916,
      author       = {M. Bonatti and V. Pitozzi and P. Caruso and S. Pontis and
                      M. G. Pittelli and C. Frati and C. Mangiaracina and C. A. M.
                      Lagrasta and F. Quaini and S. Cantarella$^*$ and S.
                      Ottonello and G. Villetti and M. Civelli and B. Montanini
                      and M. Trevisani},
      title        = {{T}ime-course transcriptome analysis of a double challenge
                      bleomycin-induced lung fibrosis rat model uncovers {ECM}
                      homoeostasis-related translationally relevant genes.},
      journal      = {BMJ Open Respiratory Research},
      volume       = {10},
      number       = {1},
      issn         = {2052-4439},
      address      = {London},
      publisher    = {BMJ Publishing Group},
      reportid     = {DKFZ-2023-01905},
      pages        = {e001476},
      year         = {2023},
      abstract     = {Idiopathic pulmonary fibrosis (IPF) is an irreversible
                      disorder with a poor prognosis. The incomplete understanding
                      of IPF pathogenesis and the lack of accurate animal models
                      is limiting the development of effective treatments. Thus,
                      the selection of clinically relevant animal models endowed
                      with similarities with the human disease in terms of lung
                      anatomy, cell biology, pathways involved and genetics is
                      essential. The bleomycin (BLM) intratracheal murine model is
                      the most commonly used preclinical assay to evaluate new
                      potential therapies for IPF. Here, we present the findings
                      derived from an integrated histomorphometric and
                      transcriptomic analysis to investigate the development of
                      lung fibrosis in a time-course study in a BLM rat model and
                      to evaluate its translational value in relation to IPF.Rats
                      were intratracheally injected with a double dose of BLM
                      (days 0-4) and sacrificed at days 7, 14, 21, 28 and 56.
                      Histomorphometric analysis of lung fibrosis was performed on
                      left lung sections. Transcriptome profiling by RNAseq was
                      performed on the right lung lobes and results were compared
                      with nine independent human gene-expression IPF studies.The
                      histomorphometric and transcriptomic analyses provided a
                      detailed overview in terms of temporal gene-expression
                      regulation during the establishment and repair of the
                      fibrotic lesions. Moreover, the transcriptomic analysis
                      identified three clusters of differentially coregulated
                      genes whose expression was modulated in a time-dependent
                      manner in response to BLM. One of these clusters, centred on
                      extracellular matrix (ECM)-related process, was
                      significantly correlated with histological parameters and
                      gene sets derived from human IPF studies.The model of lung
                      fibrosis presented in this study lends itself as a valuable
                      tool for preclinical efficacy evaluation of new potential
                      drug candidates. The main finding was the identification of
                      a group of persistently dysregulated genes, mostly related
                      to ECM homoeostasis, which are shared with human IPF.},
      keywords     = {Interstitial Fibrosis (Other)},
      cin          = {B150},
      ddc          = {610},
      cid          = {I:(DE-He78)B150-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37730279},
      doi          = {10.1136/bmjresp-2022-001476},
      url          = {https://inrepo02.dkfz.de/record/282916},
}