PhD defence H. Habibie

Osteoprotegerin, RANKL and extra cellular matrix intersection in fibrosis

The research of Habibie Habibie shows that osteoprotegerin (OPG) is involved in fibrosis development, possibly via its interaction with RANKL and extracellular matrix proteins, and has potential properties as a prognostic biomarker for idiopathic pulmonary fibrosis (IPF). 

Fibrosis is defined by abundant deposition of collagen and other extracellular matrix (ECM) proteins in tissue resulting in permanent scarring and destruction of these tissues. To date, limited treatment options exist for fibrosis patients and organ transplantation is the only curative option for patients with advanced disease. Therefore, novel therapeutic modalities to cure fibrosis and biomarkers to detect or predict the progression of disease are urgently needed to provide better clinical management for patients. The results of this thesis show that osteoprotegerin is upregulated as a response to fibrotic stimuli, such as transforming growth factor-β, in both liver and lung or is upregulated when ECM stiffness increases due to fibrosis development. OPG may contribute to the progression of fibrosis and other lung diseases via inhibition of RANKL-induced type II epithelial cell proliferation, an important event in lung tissue repair and regeneration. Moreover, aberrant production of OPG can be detected in serum of patients with idiopathic pulmonary fibrosis and these serum OPG levels are linked to progression of lung fibrosis. This is an important finding since information on the likelihood of disease progression is essential as it can guide clinicians to tailor clinical management of patients with lung fibrosis.

Promotors: prof. dr. B.N. (Barbro) Melgert, prof. dr. J.K. (Janette) Burges