Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis

Ying Wei, Wenting Dong, Julia Jackson, Tsung Che Ho, Claude Jourdan Le Saux, Alexis Brumwell, Xiaopeng Li, Julia Klesney-Tait, Max L. Cohen, Paul J. Wolters, Harold A. Chapman

Research output: Contribution to journalArticlepeer-review

Abstract

We recently identified epigallocatechin gallate (EGCG), a trihydroxyphenolic compound, as a dual inhibitor of lysyl oxidase-like2 and transforming growth factor-β1 (TGFβ1) receptor kinase that when given orally to patients with idiopathic pulmonary fibrosis (IPF) reversed profibrotic biomarkers in their diagnostic biopsies. Here, we extend these findings to advanced pulmonary fibrosis using cultured precision-cut lung slices from explants of patients with IPF undergoing transplantation. During these experiments, we were surprised to discover that not only did EGCG attenuate TGFβ1 signalling and new collagen accumulation but also activated matrix metalloproteinase-dependent collagen I turnover, raising the possibility of slow fibrosis resolution with continued treatment.

Original languageEnglish (US)
Pages (from-to)729-732
Number of pages4
JournalThorax
Volume76
Issue number7
DOIs
StatePublished - Jul 1 2021
Externally publishedYes

Keywords

  • interstitial fibrosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Fingerprint

Dive into the research topics of 'Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis'. Together they form a unique fingerprint.

Cite this