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

被引：36

作者：

Wei, Ying ^{[1
]}

Dong, Wenting ^{[1
]}

Jackson, Julia ^{[2
]}

Ho, Tsung-Che ^{[1
]}

Le Saux, Claude Jourdan ^{[1
]}

Brumwell, Alexis ^{[1
]}

Li, Xiaopeng ^{[3
]}

Klesney-Tait, Julia ^{[4
]}

Cohen, Max L. ^{[1
]}

Wolters, Paul J. ^{[1
]}

Chapman, Harold A. ^{[1
,5
]}

机构：

[1] Univ Calif San Francisco, Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA

[2] Chan Zuckerberg Biohub, Infect Dis & Cell Atlas Initiat, San Francisco, CA USA

[3] Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA

[4] Univ Iowa, Internal Med, Roy J & Lucille Carver Coll Med, Iowa City, IA USA

[5] Cardiovasc Res Inst, San Francisco, CA USA

来源：

THORAX | 2021年 / 76卷 / 07期

关键词：

COPD exacerbations; exercise; pulmonary rehabilitation; ACUTE EXACERBATIONS; QUADRICEPS MUSCLE;

D O I：

10.1136/thoraxjnl-2020-215745

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

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.

引用

页码：729 / 732

页数：4

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