Remodelling-related molecular profiles in interstitial pulmonary fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) is the most representative of the idiopathic interstitial pneumonia group (IIP) and is a disease characterized by an overall poor prognosis and unresponsiveness to currently available therapies. Thus elucidation of molecular pathways to gain better insight into the pathogenesis and identify potential therapeutic targets is warranted.

Methods: We performed compartment-specific analyses using laser microdissection, RT-PCR based microarray techniques and immunohistochemistry in lung samples from well defined patients with UIP, nonspecific interstitial pneumonia (NSIP), organizing pneumonia (OP) patterns and controls (n=5 of each group).

Results: Notably, we identified cardinal regulatory genes that were specifically up-regulated in UIP (BMP 4 and MMP13), NSIP (BMP6 and CXCR4) and OP (BMP1, IL-13 and TGFB3), respectively. In UIP, remodelled areas in showed a prominent up-regulation of fibrosis-associated genes like BMP7, MMP2 and TIMP2, while non-remodelled zones were characterized by a significantly higher expression of BMP6 and pro-inflammatory mediators IL-8 and IL-17A.

Conclusions: Our findings show that the histopathological changes seen in distinct IPF entities correlate to with specific genetic alterations. As novel treatments – like the infusion of anti-fibrotic BMPs – have shown promising results in animal experiments and preliminary human studies, our results could help to develop new interventions matched to specific disease entities.