Headerimage D. Matrix Regulation

D. Matrix Regulation

Matrix Regulation and Fibrosis

Research Area Leaders

Prof. Dr. Liliane Schäfer

  • Institute of Pharmacology & Toxicology
  • Goethe University Frankfurt
    Theodor-Stern-Kai 7
    60590 Frankfurt/Main
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Prof. Dr. Andreas Günther

  • Director DPLD Program
  • Dept. of Internal Medicine
  • Justus-Liebig-University Giessen
    Medical Chair Lung Center Waldhof Elgershausen
    Klinikstrasse 33
    35392 Giessen
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Faculty involved

S. Bellusci, T. Braun, W. Eberhardt, I. Fleming, H.A. Ghofrani, V. Grau, F. Grimminger, A. Günther, H. Hackstein, C.W. Hamm, W. Kummer, J. Lohmeyer, P. Markart, R.E. Morty, U. Müller-Ladner, J. Pfeilschifter, K.T. Preissner, S.S. Pullamsetti, C. Ruppert, L. Schäfer, W. Seeger, R.T. Schermuly, K.D. Schlüter, M. Wygrecka

 

Subject

Area D focuses on the pathogenic processes underlying diffuse parenchymal lung disease (DPDL); with idiopathic lung fibrosis (IPF) as the prototypic entity, as well as heart and renal fibrosis.

A unifying concept was develped based on the findings of the preceding funding period, where we hypothesised that the loss of parenchymla cells (e.g. alveolar epithelial type II cells in IPF) represents a key trigger Event, that is then amplified by secondary processes, thus provoking adaptive, regenerative and maladaptive cellular Responses and the recruitment of circulating mesenchymal cells. This finally results in the Initiation of fibrosis by various profibroticsignalling pathways. Following this concept we will now

  1. investigate endoplasmic reticulum and lysosomal stress as key triggers of epithelial apoptosis and fibrosis,
  2. assess the interplay between lung infection and fibrosis as amplifying process, and
  3. study FGF- and Notch-related signalling with regard to incomplete epithelial regeneration and lipofibroblast-myofibroblast transition. With regard to cell-matrix interactions, we will focus on integrins, DMBT1, SMOC1 (and its regulation by miR-223) and biglycan. Synovial fibroblasts and bone marrow-derived fibrocytes as well as epithelial-to- mesenchymal transition (EMT) will be analysed with respect to local (myo)fibroblast enrichment. With regard to pro- and anti-fibrotic signalling pathways, we will
  4. focus on the DDAH–iNOS-ROS and the sGC-cGMP-PDE axes, and the role of LRP-1. Ultimately, we will harness exogenous stem/progenitor cells for novel regenerative treatment strategies in IPF/DPDL, and clinical trials will encompass the inhalative administration of heparin, urokinase and KGF and the further promotion of the recombinant surfactant-protein-B-urokinase hybrid molecule.