Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis
- 20 January 2021
- Vol. 76 (7), 729-732
- https://doi.org/10.1136/thoraxjnl-2020-215745
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.Keywords
Funding Information
- Center for Scientific Review (R01 HL142265 (H.A.C.), R21 AG052744 (C.J.-L.-S.), R35 HL150767 (H.A.C.))
- Three Lakes Foundation (Not applicable)
This publication has 18 references indexed in Scilit:
- JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental studyThorax, 2018
- Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosisJCI Insight, 2017
- Bedside Assessment of Quadriceps Muscle by Ultrasound after Admission for Acute Exacerbations of Chronic Respiratory DiseaseAmerican Journal of Respiratory and Critical Care Medicine, 2015
- An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trialBMJ, 2014
- Acute Skeletal Muscle Wasting in Critical IllnessJAMA, 2013
- Quadriceps wasting and physical inactivity in patients with COPDEuropean Respiratory Journal, 2012
- Resistance Training Prevents Deterioration in Quadriceps Muscle Function During Acute Exacerbations of Chronic Obstructive Pulmonary DiseaseAmerican Journal of Respiratory and Critical Care Medicine, 2010
- Budesonide/formoterol effects on metalloproteolytic balance in TGFβ-activated human lung fibroblastsRespiratory Medicine, 2009
- Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary diseaseThorax, 2007
- Disuse atrophy and exercise rehabilitation in humans profoundly affects the expression of genes associated with the regulation of skeletal muscle massThe FASEB Journal, 2004