Scientists of the Comprehensive Pneumology Center (CPC) at the Helmholtz Zentrum München have identified a new mechanism which contributes to the development of idiopathic pulmonary fibrosis (IPF). They showed that the pathological changes of lung tissue are accompanied by an increase in protein turnover by the central protein degradation machinery of the cell – the proteasome.
Idiopathic pulmonary fibrosis is a very aggressive form of pulmonary fibrosis and has a particularly poor prognosis. This fatal disease, for which so far no causal therapies exist, is characterized by a massive deposition of connective and scar tissue in the lung, which leads to a progressive loss of lung function and ultimately death. Connective tissue is mainly produced by myofibroblasts. The research group led by PD Dr. Silke Meiners of the Institute of Lung Biology and the CPC showed now for the first time that the activation of these myofibroblasts depends on increased protein turnover by the 26S proteasome.
In the recently published study, the Helmholtz scientists were able to demonstrate an activation of the 26S proteasome during the transformation of normal fibroblasts into myofibroblasts both in vitro and in vivo using two different experimental models of pulmonary fibrosis. Moreover, increased protein turnover was also detected in fibrotic lung tissue of IPF patients. “Conversely, we were able to show that targeted inhibition of the 26S proteasome prevents the differentiation of primary human lung fibroblasts into myofibroblasts, confirming the essential role of enhanced proteasomal protein degradation for this pathological process,” said Silke Meiners.
“Understanding the mechanisms that lead to a disease such as IPF helps us identify innovative approaches that allow therapeutic intervention,” comments Professor Oliver Eickelberg, director of the Institute of Lung Biology and scientific director of the CPC. In further studies, the Helmholtz scientists want to test the therapeutic use of substances which specifically inhibit the 26S proteasome, but do not affect other proteasome complexes in the cell. Helmholtz Zentrum München