Lysyl Oxidases: Cause Of Collagen I Matrix Remodelling In Idiopathic Pulmonary Fibrosis?

G. Tjin, T. Jegathees, A. Mahar, E. Pw Kable, J. K Burgess

Research output: Contribution to journalMeeting AbstractAcademic

Abstract

Aim: The development of fibrosis in Idiopathic Pulmonary Fibrosis (IPF) is a key feature and challenge in the treatment of the disease. The mechanisms of collagen I (COL1) reorganisation in the development of fibrosis, which may alter the stiffness of the tissue, are not well understood. Fibrillar COL1 has second harmonic generation (SHG) properties. SHG signals are coherent, propagating both in the forward (F) (primarily organized/mature collagen) and backward (B) (primarily disorganized/immature collagen) directions relative to the incident light. Collagen fibre maturity is governed by the degree of crosslinking and catalysed by enzymes from the Lysyl Oxidase family (LOX, LOXL1- 4), which are implicated IPF pathology. The aim of this study was to investigate collagen I structural remodelling and the pathological role of Lysyl Oxidases in the development of fibrosis in IPF. Methods: Formalin-fixed-and-paraffin-embedded parenchymal tissues from non-diseased donors (n = 8) and IPF explanted lungs (n = 8) were analysed for SHG. F/B SHG signal ratio was used to determine the proportion of organized to disorganized collagen. Immunohistochemistry detected LOX and LOXL1 levels in tissues with single-blinded analysis to quantify colorimetric staining by computer-assisted image-analysis. Results: Increased F/B ratio was observed in IPF compared to non-diseased tissues (p = 0.034) indicating increased COL1 fibre maturity in IPF. There was decreased LOX (p = 0.009) and increased LOXL1 (p = 0.031) expression in IPF. In lung tissues LOX negatively correlated with F/B ratio (p = 0.0491, r2= 0.249, n = 16), while LOXL1 positively correlated with F/B ratio (p = 0.003, r2= 0.4898, n = 16). Conclusion: Increased levels of COL1 fibre maturity in IPF could contribute to the increased stiffness of the tissue. LOXL1, but not LOX, may regulate the increased collagen fibre maturity in IPF tissues. These findings indicate there may be a specific role for LOX family members in the development of fibrosis in IPF.
Original languageEnglish
Pages (from-to)88
Number of pages1
JournalRespirology
Volume20
Issue number2
DOIs
Publication statusPublished - 1-Mar-2015

Keywords

  • collagen type 1
  • protein lysine 6 oxidase
  • collagen
  • paraffin
  • formaldehyde
  • enzyme
  • society
  • fibrosing alveolitis
  • Australia and New Zealand
  • Australian
  • New Zealand
  • tissues
  • maturity
  • fibrosis
  • fiber
  • collagen fiber
  • rigidity
  • donor
  • lung parenchyma
  • lung
  • pathology
  • image analysis
  • computer
  • staining
  • immunohistochemistry
  • cross linking

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