TY  - JOUR
A1  - Kim, Hyun-Taek
A1  - Yin, Wenguang
A1  - Jin, Young-June
A1  - Panza, Paolo
A1  - Gunawan, Felix
A1  - Grohmann, Beate
A1  - Büttner, Carmen
A1  - Sokol, Anna
A1  - Preussner, Jens
A1  - Günther, Stefan
A1  - Kostin, Sawa
A1  - Ruppert, Clemens
A1  - Bhagwat, Aditya M.
A1  - Ma, Xuefei
A1  - Graumann, Johannes
A1  - Looso, Mario
A1  - Günther, Andreas
A1  - Adelstein, Robert S.
A1  - Offermanns, Stefan
A1  - Stainier, Didier
T1  - Myh10 deficiency leads to defective extracellular matrix remodeling and pulmonary disease
T2  - Nature Communications
N2  - Impaired alveolar formation and maintenance are features of many pulmonary diseases that are associated with significant morbidity and mortality. In a forward genetic screen for modulators of mouse lung development, we identified the non-muscle myosin II heavy chain gene, Myh10. Myh10 mutant pups exhibit cyanosis and respiratory distress, and die shortly after birth from differentiation defects in alveolar epithelium and mesenchyme. From omics analyses and follow up studies, we find decreased Thrombospondin expression accompanied with increased matrix metalloproteinase activity in both mutant lungs and cultured mutant fibroblasts, as well as disrupted extracellular matrix (ECM) remodeling. Loss of Myh10 specifically in mesenchymal cells results in ECM deposition defects and alveolar simplification. Notably, MYH10 expression is downregulated in the lung of emphysema patients. Altogether, our findings reveal critical roles for Myh10 in alveologenesis at least in part via the regulation of ECM remodeling, which may contribute to the pathogenesis of emphysema.
KW  - Developmental biology
KW  - Extracellular matrix
KW  - Respiratory tract diseases
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50121
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-501219
SN  - 2041-1723
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 9
IS  - 1, Art. 4600
SP  - 1
EP  - 13
PB  - Nature Publishing Group UK
CY  - [London]
ER  -