scholarly journals Cellular feedback dynamics and multilevel regulation driven by the hippo pathway

2021 ◽  
Author(s):  
Jiwon Park ◽  
Carsten Gram Hansen
Keyword(s):  
Hippo Pathway ◽  
Biologically Active ◽  
Future Research ◽  
Active Components ◽  
Dynamic Activity ◽  
Developmental Defects ◽  
Multiple Substrates ◽  
Spatio Temporal ◽  
The Hippo Pathway ◽  
Multilevel Regulation

The Hippo pathway is a dynamic cellular signalling nexus that regulates differentiation and controls cell proliferation and death. If the Hippo pathway is not precisely regulated, the functionality of the upstream kinase module is impaired, which increases nuclear localisation and activity of the central effectors, the transcriptional co-regulators YAP and TAZ. Pathological YAP and TAZ hyperactivity consequently cause cancer, fibrosis and developmental defects. The Hippo pathway controls an array of fundamental cellular processes, including adhesion, migration, mitosis, polarity and secretion of a range of biologically active components. Recent studies highlight that spatio-temporal regulation of Hippo pathway components are central to precisely controlling its context-dependent dynamic activity. Several levels of feedback are integrated into the Hippo pathway, which is further synergized with interactors outside of the pathway that directly regulate specific Hippo pathway components. Likewise, Hippo core kinases also ‘moonlight’ by phosphorylating multiple substrates beyond the Hippo pathway and thereby integrates further flexibility and robustness in the cellular decision-making process. This topic is still in its infancy but promises to reveal new fundamental insights into the cellular regulation of this therapeutically important pathway. We here highlight recent advances emphasising feedback dynamics and multilevel regulation of the Hippo pathway with a focus on mitosis and cell migration, as well as discuss potential productive future research avenues that might reveal novel insights into the overall dynamics of the pathway.

scholarly journals SAT-LB78 TSH Is a Negative Modulator of Hippo Transcriptional Effectors

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Celia Fernández-Méndez ◽  
Pilar Santisteban
Keyword(s):  
Thyroid Gland ◽  
Hippo Pathway ◽  
Thyroid Tissue ◽  
Tissue Growth ◽  
Human Thyroid ◽  
In Vivo Model ◽  
Future Research ◽  
Follicular Cells ◽  
Thyroid Follicular Cells ◽  
The Hippo Pathway

Abstract Hippo signaling pathway regulation by hormonal signals acting through G-coupled receptors has been widely described. Modulation of processes such as tissue growth or differentiation by this pathway critically relies on the location and levels of its major effectors: the cofactors YAP/TAZ and the family TEAD of transcription factors. Despite this well-defined regulatory mechanism, little is known about the Hippo pathway in the thyroid gland. Thyrotropin (TSH), main factor for thyroid follicular cells differentiation, plays its role by interacting with its G-protein-coupled receptor (TSHR). High serum TSH levels are associated with hypothyroidism, characterized by a change in thyroid follicle morphology and inflammation of the thyroid gland. This led us to study if TSH could modulate the Hippo pathway.Rat thyroid follicular cells (PCCl3) were treated with TSH and forskolin, an adenylyl cyclase activator. By immunofluorescence and western blot, levels and subcellular location of the Hippo Pathway components were assessed in different conditions. An increase of the Hippo kinase MST1/2 and LATS1/2 was observed after TSH and forskolin treatments, corresponding to a downregulation of the transcriptional mediators of the pathway TAZ, YAP and Tead1. Especially remarkable is the translocation of YAP/TAZ from the nucleus, which involves a decrease in their activity.Next, we validated the results in an in vivo model generating hypothyroidism in 3-month-old male C57BL/6J by adding MMI (2-Mercapto-1-Methylimidazole) and perchlorate (KClO4) to their drinking water. After 2 weeks of treatment, we euthanized the animals, validated higher TSH serum levels and performed analysis of the Hippo components in the thyroid by immunohistochemistry. A reduction in the levels of the Hippo effectors TAZ, YAP and Tead1 was found in the thyroid slices from hypothyroid mice, confirming the in vitro results. In addition, evaluation of a human thyroid tissue microarray, including Hashimoto disease samples, led to a validation of the previously described TSH role.Hereby, we report a crosstalk by which TSH is increasing the kinase axis of the Hippo pathway thus decreasing the activity of its main transcriptional effectors in the nuclei. Future research of the role of these transcriptional effectors will be carry out to discern if their decrease could be associated with the morphology changes linked to hypothyroidism.

scholarly journals The Fruit Malus prunifolia (Malus micromalus Mak.): A Minireview of Current Knowledge of Fruit Composition and Health Benefits

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Xiaolong Ji ◽  
Chunyan Hou ◽  
Xudan Guo
Keyword(s):  
Yellow River ◽  
Current Knowledge ◽  
Biological Activities ◽  
Biologically Active ◽  
Future Research ◽  
Active Components ◽  
Medicinal Uses ◽  
Malus Prunifolia ◽  
Rosaceae Family ◽  
Phytochemical Studies

The fruit Malus prunifolia (Malus micromalus Mak.), which belongs to the Rosaceae family, grows mostly in the upper-middle reaches of the Yellow River area. It has long been popular as a fruit commodity and as a natural remedy. Its main biologically active components include vitamin C, phenolics, flavonoids, polysaccharides, and triterpenic acids. Recent phytochemical studies on the fruit have shed some light on its biological activities, such as anticancer, immunomodulatory, antioxidant, immunostimulating, hepatoprotective, and gastrointestinal protective activities. A stronger focus on clinical studies and phytochemical characterization of the fruit will be essential for future research efforts. This minireview could be useful for predicting its other medicinal uses and its potential drug or food interactions, and it could be beneficial for people living in areas where the fruit is endemic and where healthcare resources are scarce.

scholarly journals YAP and TAZ are required for the postnatal development and the maintenance of the structural integrity of the oviduct

Reproduction ◽  
2020 ◽  
Vol 160 (2) ◽  
pp. 307-318
Author(s):  
Philippe Godin ◽  
Mayra Tsoi ◽  
Marilène Paquet ◽  
Derek Boerboom
Keyword(s):  
Postnatal Development ◽  
Reproductive Tract ◽  
Structural Integrity ◽  
Hippo Pathway ◽  
Female Reproductive Tract ◽  
Mullerian Duct ◽  
Developmental Defects ◽  
Müllerian Duct ◽  
And Function ◽  
The Hippo Pathway

The development of the Müllerian ducts into the female reproductive tract requires the coordination of multiple signaling pathways that regulate proliferation, apoptosis and differentiation. The Hippo pathway has been reported to interact with several pathways with established roles in Müllerian duct development; yet, its potential roles in reproductive tract development and function remain mostly uncharacterized. The objective of this study was therefore to characterize the roles of the Hippo transcriptional coactivators YAP and TAZ in the female reproductive tract using transgenic mouse models. This report shows that the concomitant conditional inactivation of Yap and Taz in the mouse Müllerian duct mesenchyme results in postnatal developmental defects of the oviduct. Most notably, discontinuities in the myosalpinx layer lead to the progressive formation of cystic dilations of the isthmus. These defects prevented embryo transport and subsequent implantation in older animals, causing infertility. The loss of YAP/TAZ did not appear to affect other biological processes known to be required for the maintenance of oviductal wall integrity, such as TGF-β/SMAD and Notch signaling and the biogenesis of miRNA, suggesting that the Hippo pathway acts independently of these processes to direct oviduct development. Taken together, these results suggest redundant and essential roles for YAP and TAZ in the postnatal development of the oviduct and the maintenance of its structural integrity.

scholarly journals The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhuo Xie ◽  
Ying Wang ◽  
Guang Yang ◽  
Jing Han ◽  
Liguo Zhu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Hippo Pathway ◽  
Gastrointestinal Diseases ◽  
Future Research ◽  
Inflammatory Disorder ◽  
Inflammatory Bowel ◽  
The Hippo Pathway

AbstractInflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder that primarily comprises Crohn’s disease (CD) and ulcerative colitis (UC). Owing to its increasing prevalence in Eastern countries and the intractable challenges faced during IBD treatment, extensive research on IBD has been carried out over the last few years. Although the precise aetiology of IBD is undefined, the currently accepted hypothesis for IBD pathogenesis considers it to be a combination of environment, genetic predisposition, gut microbiota, and abnormal immunity. A recently emerged signalling pathway, the Hippo pathway, acts as a key regulator of cell growth, tissue homoeostasis, organ size, and has been implicated in several human cancers. In the past few years, studies have revealed the importance of the Hippo pathway in gastrointestinal tract physiology and gastrointestinal diseases, such as colorectal cancer and IBD. However, the role of the Hippo pathway and its exact impact in IBD remains to be elucidated. This review summarises the latest scientific literature on the involvement of this pathway in IBD from the following perspectives that account for the IBD pathogenesis: intestinal epithelial cell regeneration, immune regulation, gut microbiota, and angiogenesis. A comprehensive understanding of the specific role of the Hippo pathway in IBD will provide novel insights into future research directions and clinical implications of the Hippo pathway.

PRODUCTION OF BLENDED JUICE FROM PUMPKIN, QUINCE, PERSIMMON

2018 ◽  
pp. 59-62
Author(s):  
I. A. Kyazimova ◽  
А. А. Kasumova ◽  
А. А. Nabiev
Keyword(s):  
Phenolic Compounds ◽  
Organic Acids ◽  
New Technology ◽  
Mineral Elements ◽  
Biologically Active ◽  
Active Components ◽  
Aliphatic Acids ◽  
Free Glucose ◽  
Dietary Value ◽  
Quantitative Indicators

Production of plant products, including juices around the world increases continuously. In the fruit and vegetable juices contain a significant amount of monosaccharides (glucose and fructose), organic acids, vitamins, phenolic compounds, mineral substances and other biologically active components that determine the nutritional and dietary value. For the prevention of various diseases associated with impaired metabolic processes, we developed a new technology of preparation of food by blending juice of pumpkin, quince and persimmon. Thus prepared organic blended juice contains a substantial amount of free glucose and fructose, different phenolic compounds, a sufficient amount of organic acids, mineral elements, including iodine and other components that determine its nutritional and biological value. In prepared juices were evaluated the quantitative indicators of β-carotene, vitamin C, glucose and fructose, sucrose, starch, pectin substances. Also in the atomic absorbtion spectrometer Analyst 400 (PerkinElmer, USA) was analyzed content of the organic acids and phenolic compounds. Prepared juices were tested in accordance with 10 point scoring scale. It is established that all juices contain a sufficient amount of the minerals. In pumpkin and quince juices not contain iodine while it presents in sufficient amount in persimmon juice that’s why in the blended juice mineral in addition to mineral elements iodine are contained. In pumpkin and persimmon aliphatic acids are contained in small amount. For this reason during the blending process was used quince juice which is rich in aliphatic acids. The blended juice is light straw color, with delicious flavor, a slight astringent property and a balanced taste.

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