PhD defence R.K. (Rosa) Kortekaas

Lung epithelial progenitor responses in diseased micro-environments

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive lung disease (COPD) are both incurable lung diseases that worsen over time. The epithelium, which lines the inner surface of the lung, can normally repair itself after injury. However, in IPF and COPD, the epithelium is abnormal and its repair capacity is likely reduced. The stem cells of the epithelium, which are responsible for repair, react to signals from their environment such as growth factors and other molecules. In IPF and COPD, the composition of the molecules that are present in the stem cell environment is changed, which likely affects stem cell behavior.

In her thesis Rosa Kortekaas has therefore studied the impact of the changed environments in IPF and COPD on the repair capacity of lung epithelial stem cells. She found that IL-11, a molecule which plays a role in the development of IPF, inhibits the ability of epithelial stem cells to start the repair process, and blocks their development into mature epithelial cell subtypes.

Additionally, she has replicated the molecules present in the IPF environment using a combination of nine IPF-relevant molecules. This combination of molecules caused disturbances in the balance of the different epithelial cell subtypes.

Kortekaas also replicated the molecules present during a sudden severe worsening of COPD, and found that this stimulated the growth of the stem cells, though the balance of different epithelial cell subtypes was disturbed. In conclusion, alterations in the environments in IPF and COPD affects stem cell growth and their development into epithelial cell subtypes.

Promotores Prof.dr. R. Gosens and Prof.dr. J.K. Burgess