Scientists reveal potential therapeutic approach to idiopathic pulmonary fibrosis

Helmholtz Zentrum München - German Research Center for Environmental HealthJul 28 2015

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.

Inhibition of the proteasome as a possible therapeutic approach

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. Furthermore, the lung researchers speculate that activation of the 26S proteasome may generally occur in fibrotic diseases, such as heart and kidney fibrosis, since differentiation of fibroblasts into myofibroblasts also is the underlying mechanism for the pathological alterations in these disorders.