Blocking LOXL2 and TGF beta 1 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

doi:10.1136/thoraxjnl-2020-215745

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Blocking LOXL2 and TGF beta 1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis

Journal article

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Blocking LOXL2 and TGF beta 1 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, …

Thorax, Vol.76(7), pp.729-732

07/01/2021

DOI: 10.1136/thoraxjnl-2020-215745

PMCID: PMC8222054

PMID: 33472968

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https://www.ncbi.nlm.nih.gov/pmc/articles/8222054View

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Abstract

We recently identified epigallocatechin gallate (EGCG), a trihydroxyphenolic compound, as a dual inhibitor of lysyl oxidase-like2 and transforming growth factor-beta 1 (TGF beta 1) 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 TGF beta 1 signalling and new collagen accumulation but also activated matrix metalloproteinase-dependent collagen I turnover, raising the possibility of slow fibrosis resolution with continued treatment.

Life Sciences & Biomedicine

Respiratory System

Science & Technology

Details

Title: Subtitle: Blocking LOXL2 and TGF beta 1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis
Creators: Ying Wei - University of California, San Francisco
Wenting Dong - University of California, San Francisco
Julia Jackson - Chan Zuckerberg Biohub San Francisco
Tsung-Che Ho - University of California, San Francisco
Claude Jourdan Le Saux - University of California, San Francisco
Alexis Brumwell - University of California, San Francisco
Xiaopeng Li - Michigan State University
Julia Klesney-Tait - University of Iowa
Max L. Cohen - University of California, San Francisco
Paul J. Wolters - University of California, San Francisco
Harold A. Chapman - University of California, San Francisco
Resource Type: Journal article
Publication Details: Thorax, Vol.76(7), pp.729-732
DOI: 10.1136/thoraxjnl-2020-215745
PMID: 33472968
PMCID: PMC8222054
NLM abbreviation: Thorax
ISSN: 0040-6376
eISSN: 1468-3296
Publisher: Bmj Publishing Group
Number of pages: 4
Grant note: R01 HL142265; R35 HL150767; R21 AG052744 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Three Lakes Foundation
Language: English
Date published: 07/01/2021
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984359870602771

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