Idiopathic pulmonary fibrosis clustering based on cilium gene expression: profiling a new paradigm.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF), the commonest form of the interstitial lung diseases identifies a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults, and limited to the lungs. IPF represents an unsolved health problem with an urgent medical need due to lack of effective therapies. Although precise IPF etiology remains elusive, during the past decade there has been a shift away from the pathogenetic theory of generalized inflammation progressing to a paradigm of disordered fibroproliferation and alveolar epithelial cell function. A better understanding of the molecular mechanisms driving IPF fibroblasts proliferation is mandatory to provide insights into the pathogenesis, and to identify highly reproducible biomarkers for disease onset and progression. In this review we aim to discuss and analyze the findings recently published by Yang et al. on Thorax, which reported a strong molecular signature as-sociated with the expression of cilium genes that divides IPF/ usual interstitial pneumonia into two subtypes, one with increased cilium gene expression and one with low expression of cilium genes. The study presents a number of methodology limitations, mainly related to samples characterization and to a general overstatement of the conclusions from class clustering analysis. Nevertheless, the study clearly demonstrates ­ for the first time ­ that the cilium apparatus is activated in microscopic honeycombing. In such setting, cilia are likely to act as signaling "machine" which cooperates in promoting proliferative and regenerative cellular processes. Although preliminary, these results sustain a rationale to develop further investigations to confirm the impact of cilium gene expression in IPF with the final perspective of therapeutic intervention.