Apoptosis AND MST1

The Hippo pathway is a key regulator of tissue growth, organ size, and tumorigenesis. Activating the Hippo pathway by gene editing or pharmaceutical intervention has been proven to be a new therapeutic strategy for treatment of the Hippo pathway-dependent cancers. To now, a number of compounds that directly target the downstream effector proteins of Hippo pathway, including YAP and TEADs, have been disclosed, but very few Hippo pathway activators are reported. Here, we discovered a new class of Hippo pathway activator, YL-602, which inhibited CTGF expression in cells irrespective of cell density and the presence of serum...

UNLABELLED: The Hippo kinases MST1 and MST2 initiate a highly conserved signaling cascade called the Hippo pathway that limits organ size and tumor formation in animals. Intriguingly, pathogens hijack this host pathway during infection, but the role of MST1/2 in innate immune cells against pathogens is unclear. In this report, we generated Mst1/2 knockout macrophages to investigate the regulatory activities of the Hippo kinases in immunity. Transcriptomic analyses identified differentially expressed genes (DEGs) regulated by MST1/2 that are enriched in biological pathways, such as systemic lupus erythematosus, tuberculosis, and apoptosis...

This study observed the protective effect of resveratrol(Res) on ovarian function in poor ovarian response(POR) mice by regulating the Hippo signaling pathway and explored the potential mechanism of Res in inhibiting ovarian cell apoptosis. Female mice with regular estrous cycles were randomly divided into a blank group, a model group, and low-and high-dose Res groups(20 and 40 mg·kg~(-1)), with 20 mice in each group. The blank group received an equal volume of 0.9% saline solution by gavage, while the model group and Res groups received suspension of glycosides of Triptergium wilfordii(GTW) at 50 mg·kg~(-1) by gavage for two weeks to induce the model...

OBJECTIVES: Puerarin, the principal active constituent extracted from Pueraria, is believed to confer protection against sepsis-induced lung injury. The study aimed to elucidate the role and mechanism of Mst1/ERS in puerarin-mediated protection against acute lung injury (ALI). METHODS: Monolayer vascular endothelial cell permeability was assessed by gauging the paracellular flow of FITC-dextran 40,000 (FD40). ELISA was employed for the quantification of inflammatory cytokines...

Defective skeletal muscle regeneration is often accompanied by fibrosis. Fibroblast/adipose progenitors (FAPs) are important in these processes, however, the regulation of FAP fate decisions is unclear. Here, using inducible conditional knockout mice, we show that blocking mammalian Ste20-like kinases 1/2 (MST1/2) of FAPs prevented apoptosis and reduced interleukin-6 secretion in vivo and in vitro, which impaired myoblast proliferation and differentiation, as well as impaired muscle regeneration. Deletion of Mst1/2 increased co-localization of Yes-associated protein (YAP) with Smad2/3 in nuclei and promoted differentiation of FAPs toward myofibroblasts, resulting in excessive collagen deposition and skeletal muscle fibrosis...

Pasteurella multocida is an opportunistic zoonotic pathogen that primarily causes fatal respiratory diseases, such as pneumonia and respiratory syndromes. However, the precise mechanistic understanding of how P. multocida disrupts the epithelial barrier in mammalian lung remains largely unknown. In this study, using unbiased RNA-seq analysis, we found that the evolutionarily conserved Hippo-Yap pathway was dysregulated after P. multocida infection. Given the complexity of P. multocida infection associated with lung injury and systemic inflammatory processes, we employed a combination of cell culture models, mouse models, and rabbit models to investigate the dynamics of the Hippo-Yap pathway during P...

AIMS: Spinal cord injury (SCI) is a devastating neurological disease that often results in tremendous loss of motor function. Increasing evidence demonstrates that diabetes worsens outcomes for patients with SCI due to the higher levels of neuronal oxidative stress. Mammalian sterile 20-like kinase (MST1) is a key mediator of oxidative stress in the central nervous system; however, the mechanism of its action in SCI is still not clear. Here, we investigated the role of MST1 activation in induced neuronal oxidative stress in patients with both SCI and diabetes...

[This retracts the article DOI: 10.2147/OTT.S193787.].

Mutations in STK4 (MST1) are implicated in a form of autosomal recessive combined immunodeficiency, resulting in recurrent infections (especially Epstein-Barr virus viremia), autoimmunity, and cardiac malformations. Here we report a patient with an atypically mild presentation of this disease, initially presenting with severe T cell lymphopenia (< 500 per mm3 ) and intermittent neutropenia, but now surviving well on immunoglobulins and prophylactic antibacterial treatment. She harbors a unique STK4 mutation that lies further downstream than all others reported to date...

Tuberous sclerosis complex 1 (TSC1) plays important roles in regulating innate immunity. However, the precise role of TSC1 in macrophages in the regulation of oxidative stress response and hepatic inflammation in liver ischemia/reperfusion injury (I/R) remains unknown. In a mouse model of liver I/R injury, deletion of myeloid-specific TSC1 inhibited AKT and MST1 phosphorylation, and decreased NRF2 accumulation, whereas activated TLR4/NF-κB pathway, leading to increased hepatic inflammation. Adoptive transfer of AKT- or MST1-overexpressing macrophages, or Keap1 disruption in myeloid-specific TSC1-knockout mice promoted NRF2 activation but reduced TLR4 activity and mitigated I/R-induced liver inflammation...

AIMS: Acute myocardial infarction (MI) is a significant contributor to death in individuals diagnosed with coronary heart disease on a worldwide level. The specific mechanism by which circRbms1 contributes to the damage caused by myocardial ischaemia-reperfusion (I/R) is not well understood. The primary aim of this study was to examine the role of circRbms1 and its associated mechanisms in the setting of I/R injury. METHODS AND RESULTS: An in vivo MI mice model and an in vitro MI cell model was established...

BACKGROUND: Mammalian STE20-like kinase 1 (MST1) is involved in the occurrence of cancer and autoimmune diseases by regulating cell proliferation, differentiation, apoptosis and other functions. However, its role and downstream targets in rheumatoid arthritis (RA) remain unclear. METHODS: The model of RA fibroblast-like synoviocytes (RA-FLSs) overexpressing MST1 was constructed by lentiviral transfection in vitro and analyzed the effects of MST1 on apoptosis, migration, invasion, and inflammation of RA-FLSs...

Doxorubicin (DOX) is a popular and potent anticancer drug, but its cardiotoxicity limits its clinical application. Shikonin has a wide range of biological functions, including antioxidant and anti-inflammatory effects. The aim of this study was to investigate the effects of shikonin on DOX-induced cardiac injury and to identify the underlying mechanisms. Mice receiving shikonin showed reduced cardiac injury response and enhanced cardiac function after DOX administration. Shikonin significantly attenuated DOX-induced oxidative damage, inflammation accumulation and cardiomyocyte apoptosis...

MST1, MST2, MST3, MST4, and YSK1 are conserved members of the mammalian sterile 20-like serine/threonine (MST) family that regulate cellular functions such as proliferation and migration. The MST3 isozyme plays a role in regulating cell growth and apoptosis, and its dysregulation has been linked to high-grade tumors. To date, there are no isoform-selective inhibitors that could be used for validating the role of MST3 in tumorigenesis. We designed a series of 3-aminopyrazole-based macrocycles based on the structure of a promiscuous inhibitor...

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause joint inflammation and damage. Leonurine (LE) is an alkaloid found in Leonurus heterophyllus. It has anti-inflammatory effects. HYPOTHESIS/PURPOSE: The molecular mechanisms by which LE acts in RA are unclear and further investigation is required. METHODS: Mice with collagen-induced arthritis (CIA), and RA-fibroblast-like synoviocytes (FLSs) isolated from them were used as in vivo and in vitro models of RA, respectively...

Hypopharyngeal squamous cell carcinoma (HSCC) is a malignant tumor of head and neck. It was verified that circ0005027 was downregulated in HSCC tissues. Here, we aimed to investigate the function and specific regulatory mechanism of circ0005027 in HSCC. Ten pairs tissues of HSCC and adjacent para-cancer were collected. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) measured circ0005027, miR-548c-3p, and Cadherin 1 (CDH1) mRNA expression. CCK-8 analyzed cell proliferation viability...

PURPOSE: The risk of brain exposure to ionizing radiation increases gradually due to the extensive application of nuclear technology in medical, industrial, and aerospace fields. Radiation-induced brain injury (RBI) is highly likely to cause a wide range of neurological complications, including schizophrenia, Alzheimer's disease (AD), depression. Ginkgolide B (GB) is one of the effective active components extracted from ginkgo biloba leaves, exerts protective effects on CNS, which involved in the regulation of Hippo signaling pathway...

BACKGROUND: Lung endothelium plays a pivotal role in the orchestration of inflammatory and injury responses to acute pulmonary insults. Mammalian sterile 20-like kinase 1 (Mst1), a mammalian homolog of Hippo, is a serine/threonine kinase that is ubiquitously expressed in many tissues and has been shown to play an important role in the regulation of apoptosis, inflammation, stress responses, and organ growth. While Mst1 exhibits high expression in the lung, its involvement in the endothelial response to pulmonary insults remains largely unexplored...

OBJECTIVE: Hyperglycemia and insulin resistance or deficiency are characteristic features of diabetes. Diabetes is accompanied by cardiomyocyte hypertrophy, fibrosis and ventricular remodeling, and eventually heart failure. In this study, we established a diabetic cardiomyopathy (DCM) mouse model to explore the role and mechanism of miR-200a-3p in DCM. METHODS: We used db/db mice to simulate the animal model of DCM and the expression of miR-200a-3p was then examined by RT-qPCR...

Breast cancer is a molecularly heterogeneous disease and the most common female malignancy. In recent years, therapy approaches have evolved to accommodate molecular diversity, with a focus on more biologically based therapies to minimize negative consequences. To regulate cell fate in human breast cells, the Hippo signaling pathway has been associated with the alpha subtype of estrogen receptors. This pathway regulates tissue size, regeneration, and healing, as well as the survival of tissue-specific stem cells, proliferation, and apoptosis in a variety of organs, allowing for cell differentiation...