KFO309 - The clinical research unit Virus Induced Lung injury

Principal Investigators

Andreas Günther

Prof. Dr. med. Andreas Günther

Justus Liebig University Giessen
Department of Internal Medicine
Klinikstrasse 31; 35392 Giessen

+49-641-99-42502
Saverio Bellusci

Prof. Dr. rer. nat. Saverio Bellusci

Justus Liebig University Giessen
Excellence Cluster „Cardiopulmonary System“ 
Aulweg 130, 35392 Giessen

+49-641-99-46730
Elie El Agha

Elie El Agha , , PhD

Justus Liebig University Giessen, Aulweg 130; 35392 Giessen

Role of epithelial endoplasmic reticulum stress and epithelial FGF signaling in the initiation and aggravation of lung fibrosis by viral infection

Summary

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal parenchymal lung disease, which is proposed to originate from chronic injury to aged alveolar epithelial type 2 cells (AEC II) such as pro-apoptotic (maladaptive) endoplasmic reticulum (ER) stress. Viral infection is known to trigger progression of IPF and to aggravate the disease. Fibroblast Growth Factor 10 (FGF-10) has been shown to be important for the formation of the alveolar epithelial lineage development and for survival of AEC II in response to injury. In the preceding funding period, we could show that viral infection of AEC II undergoing maladaptive ER-stress (via CHOP) results in a boost of AEC II apoptosis and lung fibrosis, whereas adaptive ER-stress of AEC II did not. We identified the microRNA miR-142 to be linked with the formation of AEC II during lung development and to be regulated by FGF-10. Moreover, we found that FGF-10 prevents influenza virus (IV, PR8) amplification in AEC II and that a knockout of miR-142 makes AEC II more resistant to PR8. Additionally, we showed that the first-line antidiabetic drug metformin impacts FGF-10 signaling and accelerates lung regeneration after injury (Kheirollahi et al. Nat Commun, in press). Based on these results, we propose, in the forthcoming funding period, that the newly discovered FGF-10-FGFR2b-miR-142 signaling axis in the adult lung decreases viral infection of ER-stressed AEC II cells, and we envision that targeting this axis including metformin administration beneficially impacts virus-induced lung injury and regeneration. 

Publications


IRE-1 signaling as a putative therapeutic target in influenza-induced pneumonia

Am J Respir Cell Mol Biol 019 Oct;61(4):537-540. doi: 10.1165/rcmb.2019-0123LE













Principal Investigators

Andreas Günther

Prof. Dr. med. Andreas Günther

Justus Liebig University Giessen
Department of Internal Medicine
Klinikstrasse 31; 35392 Giessen

+49-641-99-42502
Saverio Bellusci

Prof. Dr. rer. nat. Saverio Bellusci

Justus Liebig University Giessen
Excellence Cluster „Cardiopulmonary System“ 
Aulweg 130, 35392 Giessen

+49-641-99-46730
Elie El Agha

Elie El Agha , , PhD

Justus Liebig University Giessen, Aulweg 130; 35392 Giessen

Project group

  • Martina Korfei

    Dr. Martina Korfei

    Postdoc

  • Irina Shalashova

    Irina Shalashova

  • Cho-Ming Chao

    Dr. Cho-Ming Chao

  • Silke Händel

    Silke Händel

    Technician

  • Simone Becker

    Simone Becker

    Technician

  • Kerstin Goth

    Kerstin Goth

    Technician