PT  - JOURNAL ARTICLE
AU  - Tjin, Gavin
AU  - Mahar, Annabelle
AU  - Kable, Eleanor
AU  - Burgess, Janette
TI  - Lysyl oxidases in idiopathic pulmonary fibrosis: A key participant in collagen I matrix remodelling
AID  - 10.1183/13993003.congress-2015.PA890
DP  - 2015 Sep 01
TA  - European Respiratory Journal
PG  - PA890
VI  - 46
IP  - suppl 59
4099  - http://erj.ersjournals.com/content/46/suppl_59/PA890.short
4100  - http://erj.ersjournals.com/content/46/suppl_59/PA890.full
SO  - Eur Respir J2015 Sep 01; 46
AB  - Introduction: The fibrotic element in Idiopathic Pulmonary Fibrosis (IPF) is a key feature and is associated with Usual Interstitial Pneumonia (UIP) pattern. Fibrillar collagen I (COL1) has second harmonic generation (SHG) properties, with signals both in the forward (F) (organized collagen) & backward (B) (disorganized collagen) directions. Collagen fibre organisation is governed by the degree of cross-linking & catalysed by enzymes from the Lysyl Oxidase family (LOX, LOXL1-4).This study aimed to investigate COL1 structural remodelling & Lysyl Oxidase levels in IPF.Methods: Formalin-fixed parenchymal tissues from two cohorts; (1) non-diseased donors (ND) (n=8) & IPF explanted lungs (n=8), (2) diagnostic biopsies (UIP=26; non-UIP=9) were analysed for SHG; F/B SHG signal ratio represented the proportion of organized to disorganized collagen. Tissue sections were immuno-stained for LOX, LOXL1 & LOXL2. Whole tissue images were captured & quantified by computerized image-analysis.Results: Increased F/B ratio in IPF vs ND (p<0.05) indicating increased COL1 fibre organisation in IPF; no difference observed for UIP vs non-UIP. LOX was decreased (p<0.05), LOXL1 increased (p<0.05) & LOXL2 increased (p<0.05) in IPF vs ND and LOXL1 was increased in UIP vs non-UIP (p<0.05). F/B ratio positively correlated with LOXL1 (p<0.05, r2=0.49, n=16) & LOXL2 (p<0.05, r2=0.33, n=16) in IPF & ND.Conclusion: Increased levels of COL1 fibre organisation detected by SHG in IPF UIP is also present in non-UIP tissues. LOXL1 & LOXL2 but not LOX may regulate collagen fibre organisation in IPF. These findings indicate LOX family members may play a specific role in the development of fibrosis in IPF.