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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kim, Miju Kinashi, Tatsuo Kim, Minchul Song, Hoogeun Kim, Tae-shin Lim, Dae-sik Hwang, Deog-su Kim, Hanbyul Seo, Eunjeong Kim, Sang Kyum Kim, Tackhoon Yoo, Geon Lee, Da-hye Chung, Chaeuk Lee, Sang-hee Kim, Jin-man |
| Description | Author Affiliation: Chung C ( Department of Biological Sciences, National Creative Research Initiatives Center, Biomedical Research Center, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.); |
| Abstract | Respiratory distress syndrome (RDS), which is induced by insufficient production of surfactant, is the leading cause of mortality in preterm babies. Although several transcription factors are known to be involved in surfactant protein expression, the molecular mechanisms and signaling pathways upstream of these transcription factors have remained elusive. Here, using mammalian Hippo kinases (Mst1/2, mammalian sterile 20-like kinase 1/2) conditional knockout mice, we demonstrate that Mst1/2 kinases are critical for orchestration of transcription factors involved in surfactant protein homeostasis and prevention of RDS. Mice lacking Mst1/2 in the respiratory epithelium exhibited perinatal mortality with respiratory failure and their lungs contained fewer type I pneumocytes and more immature type II pneumocytes lacking microvilli, lamellar bodies, and surfactant protein expression, pointing to peripheral lung immaturity and RDS. In contrast to previous findings of YAP (Yes-associated protein)-mediated canonical Hippo signaling in the liver and intestine, loss of Mst1/2 kinases induced the defects in pneumocyte differentiation independently of YAP hyperactivity. We instead found that Mst1/2 kinases stabilized and phosphorylated the transcription factor Foxa2 (forkhead box A2), which regulates pneumocyte maturation and surfactant protein expression. Taken together, our results suggest that the mammalian Hippo kinases play crucial roles in surfactant homeostasis and coordination of peripheral lung differentiation through regulation of Foxa2 rather than of YAP. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 19 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Gene Expression Regulation, Developmental Gene Expression Regulation Hepatocyte Nuclear Factor 3-beta Metabolism Protein-Serine-Threonine Kinases Genetics Pulmonary Surfactant-Associated Proteins Pneumocytes Cytology Animals Apoptosis Cell Differentiation Cell Line Cell Proliferation Crosses, Genetic Homeostasis Lung Embryology Growth & Development Mice Mice, Knockout Microscopy, Electron, Transmission Physiology Signal Transduction Time Factors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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