Lysyl oxidases in idiopathic pulmonary fibrosis: A key participant in collagen I matrix remodelling

Abstract

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 immunostained for LOX, LOXL1 & LOXL2. Whole tissue images were captured & quantified by computerized imageanalysis. Results: Increased F/B ratio in IPF vs ND (