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Blocking LOXL2 and TGFβ1 Signalling Induces Collagen I Turnover in Precision-cut Lung Slices Derived from Patients with Idiopathic Pulmonary Fibrosis

Overview
Journal Thorax
Date 2021 Jan 21
PMID 33472968
Citations 26
Authors
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
Affiliations
Soon will be listed here.
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.

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LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension.

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