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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723962.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Attenuating endogenous Fgfr2b ligands during bleomycin-induced lung fibrosis does not compromise murine lung repair
Authors:MacKenzie, B.; Henneke, I.; Hezel, S.; Al Alam, D.; El Agha, E.; Chao, C. M.; Quantius, J.; Wilhelm, J.; Jones, M.; Goth, K.; Li, X.; Seeger, W.; Konigshoff, M.; Herold, S.; Rizvanov, A. A.; Gunther, A.; Bellusci, S.
Date of Publication (YYYY-MM-DD):2015-05-15
Title of Journal:Am J Physiol Lung Cell Mol Physiol
Volume:308
Issue / Number:10
Start Page:L1014
End Page:24
Audience:Not Specified
Abstract / Description:Fibroblast growth factors (Fgfs) mediate organ repair. Lung epithelial cell overexpression of Fgf10 postbleomycin injury is both protective and therapeutic, characterized by increased survival and attenuated fibrosis. Exogenous administration of FGF7 (palifermin) also showed prophylactic survival benefits in mice. The role of endogenous Fgfr2b ligands on bleomycin-induced lung fibrosis is still elusive. This study reports the expression of endogenous Fgfr2b ligands, receptors, and signaling targets in wild-type mice following bleomycin lung injury. In addition, the impact of attenuating endogenous Fgfr2b-ligands following bleomycin-induced fibrosis was tested by using a doxycycline (dox)-based inducible, soluble, dominant-negative form of the Fgfr2b receptor. Double-transgenic (DTG) Rosa26(rtTA/+);tet(O)solFgfr2b mice were validated for the expression and activity of soluble Fgfr2b (failure to regenerate maxillary incisors, attenuated recombinant FGF7 signal in the lung). As previously reported, no defects in lung morphometry were detected in DTG (+dox) mice exposed from postnatal days (PN) 1 through PN105. Female single-transgenic (STG) and DTG mice were subjected to various levels of bleomycin injury (1.0, 2.0, and 3.0 U/kg). Fgfr2b ligands were attenuated either throughout injury (days 0-11; days 0-28) or during later stages (days 6-28 and 14-28). No significant changes in survival, weight, lung function, confluent areas of fibrosis, or hydroxyproline deposition were detected in DTG mice. These results indicate that endogenous Fgfr2b ligands do not significantly protect against bleomycin injury, nor do they expedite the resolution of bleomycin-induced lung injury in mice.
Free Keywords:Animals; Antibiotics, Antineoplastic/*adverse effects/pharmacology; Bleomycin/*adverse effects/pharmacology; Female; Fibroblast Growth Factor 7/*pharmacology; Mice; Mice, Transgenic; *Pulmonary Fibrosis/chemically induced/drug therapy/genetics/metabolism/pathology; Receptor, Fibroblast Growth Factor, Type 2/agonists/genetics/*metabolism; Signal Transduction/*drug effects/genetics
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Developmental Biology Program, Division of Surgery, Saban Research Institute of Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California; School of Pharmacy, Wenzhou Medical College, China; Comprehensive Pneumology Center, Ludwig Maximilians University, University Hospital Grosshadern, and Helmholtz Zentrum Munchen, Munich, Bavaria, Germany; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia. German Center for Lung Research, Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, Giessen, Hessen, Germany; AGAPLESION Lung Clinic Waldhof-Elgershausen, Greifenstein, Germany; German Center for Lung Research, Germany; German Center for Lung Research, Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, Giessen, Hessen, Germany; Developmental Biology Program, Division of Surgery, Saban Research Institute of Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California; Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia saverio.bellusci@innere.med.uni-giessen.de.
Identifiers:ISSN:1522-1504 (Electronic) 1040-0605 (Linking) %R 10.1152/ajplung.00291.2014
URL:http://www.ncbi.nlm.nih.gov/pubmed/25820524
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