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.
