Open AccessBlocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis
Author(s) -
Ying Wei,
Wenting Dong,
Julia R. Jackson,
T. Ho,
Claude Jourdan Le Saux,
Alexis Brumwell,
Xiaopeng Li,
Julia Klesney-Tait,
Max Cohen,
Paul J. Wolters,
Harold A. Chapman
Publication year - 2021
Publication title -
thorax
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.083
H-Index - 221
eISSN - 1468-3296
pISSN - 0040-6376
DOI - 10.1136/thoraxjnl-2020-215745
Subject(s) - medicine , idiopathic pulmonary fibrosis , pulmonary fibrosis , fibrosis , lung , lysyl oxidase , transforming growth factor , matrix metalloproteinase , lung transplantation , myofibroblast , pathology , cancer research , transforming growth factor beta , extracellular matrix , microbiology and biotechnology , biology
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.