Increased Polysialylation in Lung Tissue of Patients with Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial lung disease of unknown etiology. The disease is characterized by alveolar destruction, uncontrolled fibroblast proliferation and excess matrix production, resulting in progressive dyspnea, a decline in lung function and loss of gas exchange properties. So far, only pirfenidone has been shown to exert some efficacy in IPF and lung transplantation represents the only option to prevent death.

The aim of the present study is the analysis of potential differences in glycosylation, in particular polysialylation, of fibrotic versus control lung tissue. Polysialic acid (polySia) is a developmentally regulated homopolymer of α2,8-linked N-acetylneuraminic acid residues and is involved in the modulation of several migration as well as proliferation processes. We observed an up-regulation of the polysialyltransferases ST8SiaII and ST8SiaIV, the key enzymes of polySia biosynthesis, using quantitative real time PCR in IPF patients. In agreement with an enhanced mRNA expression level of both transferases we detected increased polySia levels in tissue samples of IPF patients in comparison to donor tissue by Western blotting. Using a glycoproteomics approach we were able to identify NCAM as the polySia carrier which could be confirmed by Western blot analysis. Surprisingly, polySia-NCAM was located intracellularly in vesicles of ciliated bronchiolar epithelial cells as well as clara cells. However, the role of polySia-NCAM in the bronchoalveolar system and especially during the development and the pathophysiology of IPF needs to be further investigated.