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Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Matrix+Biol 2019 ; 80 (ä): 14-28 Nephropedia Template TP
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Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis #MMPMID29933044
Bell TJ; Brand OJ; Morgan DJ; Salek-Ardakani S; Jagger C; Fujimori T; Cholewa L; Tilakaratna V; Östling J; Thomas M; Day AJ; Snelgrove RJ; Hussell T
Matrix Biol 2019[Jul]; 80 (ä): 14-28 PMID29933044show ga
Little is known about the impact of viral infections on lung matrix despite its important contribution to mechanical stability and structural support. The composition of matrix also indirectly controls inflammation by influencing cell adhesion, migration, survival, proliferation and differentiation. Hyaluronan is a significant component of the lung extracellular matrix and production and degradation must be carefully balanced. We have discovered an imbalance in hyaluronan production following resolution of a severe lung influenza virus infection, driven by hyaluronan synthase 2 from epithelial cells, endothelial cells and fibroblasts. Furthermore hyaluronan is complexed with inter-?-inhibitor heavy chains due to elevated TNF-stimulated gene 6 expression and sequesters CD44-expressing macrophages. We show that intranasal administration of exogenous hyaluronidase is sufficient to release inter-?-inhibitor heavy chains, reduce lung hyaluronan content and restore lung function. Hyaluronidase is already used to facilitate dispersion of co-injected materials in the clinic. It is therefore feasible that fibrotic changes following severe lung infection and inflammation could be overcome by targeting abnormal matrix production.