The internationally renowned scientists Prof. Dr. Antje Prasse, Dr. Benedikt Jäger and their team have carried out research at BREATH, the Hanover site of the German Center for Lung Research (DZL), for many years on the subject of pulmonary fibrosis. In their newest publication, the working group has delivered groundbreaking new findings on idiopathic pulmonary fibrosis. Their work has just been published in the renowned specialist journal „Nature Communications“ (DOI: 10.1038/s41467-022-33193-0).
Idiopathic pulmonary fibrosis (IPF) leads to chronic scarring and shrinking of the lung. Patients with IPF die on average within 3-5 years after diagnosis. The help provided by previously available drug treatment has been inadequate. One reason for this is the poor understanding up to now of the underlying mechanisms of this deadly disease.
At BREATH (Biomedical Research in Endstage and Obstructive Lung Disease), Prof. Dr. Antje Prasse and Dr. Benedikt Jäger have carried out research for many years in the field of pulmonary fibrosis. With the help of their team and their local and international cooperation partners, they have now been able to demonstrate for the first time the key role of the basal cells of the airways (bronchi) in idiopathic pulmonary fibrosis. The gene expression of these bronchial basal cells is markedly altered in patients with IPF and these cells promote fibrotic processes due to their atypical behavior and altered differentiation. In the 3D-organoid model, IPF basal cells, compared to basal cells from healthy test subjects, more closely resemble organoids such as de novo bronchial structures, lung development and carcinogenesis processes. In addition, they induce the proliferation of fibroblasts and the deposit of extracellular matrix in the co-culture. Furthermore, the working group developed a completely new mouse model for IPF, based on human basal cells from IPF patients and which thus illustrates the disease better than previous models. The international team was able to create prediction models on the basis of gene expression data from bioinformatic analyses, which forecast therapy response. Based on these In-silico analyses, among other things the SRC signal path was identified as a driving factor.
The researchers were able to show that the SRC inhibitor Saracatinib, in its newly developed in vitro and in vivo models, therapeutically downregulates the emerging fibrosis. These findings establish basal cells as key cells in the pathogenesis of human idiopathic pulmonary fibrosis and thus as a novel cellular target for the development of new therapeutic measures. „With this work we have been able to give IPF research a big push towards better treatability. We will build on this project and at some point hope to be able to offer those affected a causal therapy“, says Prof. Prasse.
This work has been published as an Open Access article in the renowned specialist journal „Nature Communications“, giving all IPF researchers worldwide the possibility to build on the latest results. The paper can be viewed here.
Jaeger, B., Schupp, J.C., Plappert, L. et al. Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis. Nat Commun 13, 5637 (2022). https://doi.org/10.1038/s41467-022-33193-0
Text: FraunhoferITEM/ Nastevska and BREATH/AB Photo: MHH/Figiel