ArticleProceedings of the National Academy of Sciences of the United States of America2013
Hippo-Foxa2 signaling pathway plays a role in peripheral lung maturation and surfactant homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Pooled it
- Effects of LATS1/2 kinases inhibition on lung epithelial cells in a regeneration model.Molecular and cellular biochemistry · 2026Article
- Mitochondrial Pyruvate Metabolism Controls Alveolar Stem Cell Fate and Inflammatory Balance.Inflammation · 2026Article
- Refractory Lung Diseases: From Cellular Structures, Molecular Mechanisms to Therapeutic Strategies.Pediatric discovery · 2026Review
- Lung scRNA-seq reveals chronic inflammation and emphysemous phenotype in mice with osteogenesis imperfecta.Frontiers in genetics · 2026Article
- Influence of intersignaling crosstalk on the intracellular localization of YAP/TAZ in lung cells.Cell communication and signaling : CCS · 2024Review
- The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress.Experimental & molecular medicine · 2024Article
- Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration.Nature communications · 2023Article
- YAP/TAZ as master regulators in cancer: modulation, function and therapeutic approaches.Nature cancer · 2023Review
- Hippo pathway in intestinal diseases: focusing on ferroptosis.Frontiers in cell and developmental biology · 2023Review
- Neonatal lung-derived SSEA-1iScience · 2022Article
- Article
- Genome-wide expression of the residual lung reacting to experimental Pneumonectomy.BMC genomics · 2021Article
- Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration.Cell stem cell · 2021Article
- SOX9 has distinct roles in the formation and progression of different non-small cell lung cancer histotypes.The Journal of pathology · 2021Article
- Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice.International journal of molecular sciences · 2021Article
- Inactivation of Lats1 and Lats2 highlights the role of hippo pathway effector YAP in larynx and vocal fold epithelium morphogenesis.Developmental biology · 2021Article
- Targeting YAP-p62 signaling axis suppresses the EGFR-TKI-resistant lung adenocarcinoma.Cancer medicine · 2021Article
- Transcriptional Response of Ovine Lung to Infection with Jaagsiekte Sheep Retrovirus.Journal of virology · 2019Article
- Taiji: System-level identification of key transcription factors reveals transcriptional waves in mouse embryonic development.Science advances · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.