Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

被引：196

作者：

El Agha, Elie ^{[1
,2
,3
]}

Moiseenko, Alena ^{[1
,2
,3
]}

Kheirollahi, Vahid ^{[1
,2
,3
]}

De langhe, Stijn ^{[4
]}

Crnkovic, Slaven ^{[5
]}

Kwapiszewska, Grazyna ^{[5
]}

Kosanovic, Djuro ^{[1
,2
,3
]}

Schwind, Felix ^{[1
,2
,3
]}

Schermuly, Ralph T. ^{[1
,2
,3
]}

Henneke, Ingrid ^{[1
,2
,3
]}

MacKenzie, BreAnne ^{[1
,2
,3
]}

Quantius, Jennifer ^{[1
,2
,3
]}

Herold, Susanne ^{[1
,2
,3
]}

Ntokou, Aglaia ^{[1
,2
,3
,6
]}

Ahlbrecht, Katrin ^{[1
,2
,3
,6
]}

Morty, Rory E. ^{[1
,2
,3
,6
]}

Guenther, Andreas ^{[1
,2
,3
]}

Seeger, Werner ^{[1
,2
,3
,6
]}

Bellusci, Saverio ^{[1
,2
,3
,7
]}

机构：

[1] Univ Giessen, Excellence Cluster Cardiopulm Syst, Lung Ctr, D-35392 Giessen, Germany

[2] Univ Marburg, Excellence Cluster Cardiopulm Syst, Lung Ctr, D-35392 Giessen, Germany

[3] Justus Liebig Univ Giessen, German Ctr Lung Res, D-35392 Giessen, Germany

[4] Natl Jewish Hlth, Div Cell Biol, Dept Pediat, Denver, CO 80206 USA

[5] Ludwig Boltzmann Inst Lung Vasc Res, Med Res Ctr, A-8010 Graz, Austria

[6] WG Kerckhoff Inst, Max Planck Inst Heart & Lung Res, D-61231 Bad Nauheim, Germany

[7] Wenzhou Univ, Coll Life & Environm Sci, Wenzhou, Zhejiang, Peoples R China

来源：

CELL STEM CELL | 2017年 / 20卷 / 02期

关键词：

SMOOTH-MUSCLE-CELLS; PULMONARY-FIBROSIS; STEM-CELLS; GROWTH; DIFFERENTIATION; LIPOFIBROBLAST; FIBROBLAST-GROWTH-FACTOR-10; MYOFIBROBLAST; FIBROCYTES; PROTEIN;

D O I：

10.1016/j.stem.2016.10.004

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Idiopathic pulmonary fibrosis (IPF) is a form of progressive interstitial lung disease with unknown etiology. Due to a lack of effective treatment, IPF is associated with a high mortality rate. The hallmark feature of this disease is the accumulation of activated myofibroblasts that excessively deposit extracellular matrix proteins, thus compromising lung architecture and function and hindering gas exchange. Here we investigated the origin of activated myofibroblasts and the molecular mechanisms governing fibrosis formation and resolution. Genetic engineering in mice enables the time-controlled labeling and monitoring of lipogenic or myogenic populations of lung fibroblasts during fibrosis formation and resolution. Our data demonstrate a lipogenic-to-myogenic switch in fibroblastic phenotype during fibrosis formation. Conversely, we observed a myogenic-to-lipogenic switch during fibrosis resolution. Analysis of human lung tissues and primary human lung fibroblasts indicates that this fate switching is involved in IPF pathogenesis, opening potential therapeutic avenues to treat patients.

引用

页码：261 / +

页数：16

共 39 条

[1]

In search of the elusive lipofibroblast in human lungs [J].