Hippo pathway in lung development

Dai, Yuyuan; Jablons, David M.; Li, You

doi:10.21037/jtd.2017.07.18

Cited by 17 publications

(17 citation statements)

References 18 publications

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“…Additionally, many in vivo studies only focus on YAP or TAZ but do not compare the two. For example, although lung-specific conditional knockout models have been generated for many Hippo pathway components, lung-specific TAZ knockout mice have not been studied (23). Our goal was to more comprehensively characterize some of the physiological differences between YAP and TAZ in vitro in an attempt to gain greater insight into this topic.…”

Section: Discussionmentioning

confidence: 99%

The Hippo pathway effector proteins YAP and TAZ have both distinct and overlapping functions in the cell

Plouffe

Lin

Moore

et al. 2018

Journal of Biological Chemistry

189

163

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The Hippo pathway plays an important role in regulating tissue homeostasis, and its effectors, the transcriptional co-activators Yes-associated protein (YAP) and WW domain-containing transcription regulator 1 (WWTR1 or TAZ), are responsible for mediating the vast majority of its physiological functions. Although YAP and TAZ are thought to be largely redundant and similarly regulated by Hippo signaling, they have developmental, structural, and physiological differences that suggest they may differ in their regulation and downstream functions. To better understand the functions of YAP and TAZ in the Hippo pathway, using CRISPR/Cas9, we generated YAP KO, TAZ KO, and YAP/TAZ KO cell lines in HEK293A cells. We evaluated them in response to many environmental conditions and stimuli and used RNA-Seq to compare their transcriptional profiles. We found that YAP inactivation has a greater effect on cellular physiology (namely, cell spreading, volume, granularity, glucose uptake, proliferation, and migration) than TAZ inactivation. However, functional redundancy between YAP and TAZ was also observed. In summary, our findings confirm that the Hippo pathway effectors YAP and TAZ are master regulators for multiple cellular processes but also reveal that YAP has a stronger influence than TAZ.

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Section: Discussionmentioning

confidence: 99%

The Hippo pathway effector proteins YAP and TAZ have both distinct and overlapping functions in the cell

Plouffe

Lin

Moore

et al. 2018

Journal of Biological Chemistry

189

163

View full text Add to dashboard Cite

show abstract

“…13 A previous study showed that Taz mRNA expression gradually increases with advancing pregnancy during the pulmonary developmental stages from E11 to E18. 10 At E18, the same study showed that Taz mRNA expression was increased primarily in the pulmonary respiratory epithelial cells.…”

Section: F I G U R Ementioning

confidence: 87%

“…12 While the conducting airways branch and differentiate into specific cellular phenotypes, cells expressing cytoplasmic Yap are committed to a fate of becoming a part of the mature airway. 10 In a previous study, lung-specific Yap knockout mice demonstrated that pulmonary abnormalities at pseudoglandular stage started at E12. These lungs were severely hypoplastic and revealed serious destruction in the formation of branches, resulting in a dilated cystic structure.…”

Section: F I G U R Ementioning

confidence: 94%

“…When Hippo pathway is inactive, Yap/Taz are not phosphorylated, move into the nucleus, and regulate genes required for cell proliferation, differentiation, death, tissue regeneration, growth, and tumor development. 10,[49][50][51][52] Furthermore, the Hippo pathway is a critical player in the crucial steps of pulmonary development. When Hippo pathway is inactive, immature distal buds of the fetal lung develop and mature through the activation of Yap and Taz.…”

Section: F I G U R Ementioning

confidence: 99%

“…Hippo pathway is known to play an important role as a negative regulator in key steps of lung development. [9][10][11] Yap and Taz are expressed in developing pulmonary epithelial cells, which gradually increase in number throughout gestation during lung development. 12,13 In other words, immature distal buds of the fetal lung develop and mature through activation of Yap and Taz when the Hippo pathway is silent.…”

mentioning

confidence: 99%

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Melatonin for prevention of fetal lung injury associated with intrauterine inflammation and for improvement of lung maturation

Lee

Shin

et al. 2020

Journal of Pineal Research

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Inflammation is associated with injury to immature lungs, and melatonin administration to preterm newborns with acute respiratory distress improves pulmonary outcomes. We hypothesized that maternally administered melatonin may reduce inflammation, oxidative stress, and structural injury in fetal lung and help fetal lung maturation in a mouse model of intrauterine inflammation (IUI). Mice were randomized to the following groups: control (C), melatonin (M), lipopolysaccharide (LPS; a model of IUI) (L), and LPS with melatonin (ML). Pro‐inflammatory cytokines, components of the Hippo pathway, and Yap1/Taz were analyzed in the fetal lung at E18 by real‐time RT‐qPCR. Confirmatory histochemistry and immunohistochemical analyses (surfactant protein B, vimentin, HIF‐1β, and CXCR2) were performed. The gene expression of IL1β in the fetal lung was significantly increased in L compared to C, M, and ML. Taz expression was significantly decreased in L compared to C and M. Taz gene expression in L was significantly decreased compared with those in ML. Immunohistochemical analyses showed that the expression of HIF‐1β and CXCR2 was significantly increased in L compared to C, M, and ML. The area of surfactant protein B and vimentin were significantly decreased in L than C, M, or ML in the fetal and neonatal lung. Antenatal maternally administered melatonin appears to prevent fetal lung injury induced by IUI and to help lung maturation. The results from this study results suggest that melatonin could serve as a novel safe preventive and/or therapeutic medicine for preventing fetal lung injury from IUI and for improving lung maturation in prematurity.

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The hippo pathway provides novel insights into lung cancer and mesothelioma treatment

Liu

Zuo

2018

J Cancer Res Clin Oncol

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Hippo pathway in lung development

Cited by 17 publications

References 18 publications

The Hippo pathway effector proteins YAP and TAZ have both distinct and overlapping functions in the cell

The Hippo pathway effector proteins YAP and TAZ have both distinct and overlapping functions in the cell

Melatonin for prevention of fetal lung injury associated with intrauterine inflammation and for improvement of lung maturation

The hippo pathway provides novel insights into lung cancer and mesothelioma treatment

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