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BACKGROUND: Osteoarthritis is a common chronic inflammation of joints caused by degenerative changes of articular cartilage. More and more studies have shown that mechanical stress is closely related to the development of osteoarthritis. The Hippo pathway is not only involved in the development of tissue cells, but also an effecting factor of mechanical stress, which is involved in the regulation of bone metabolism and cartilage metabolism. OBJECTIVE: Regulation of the Hippo pathway may become one of the new targets for intervention in osteoarthritis. Therefore, this paper reviewed the research on the effect of mechanical stress regulation of the Hippo pathway on osteoarthritis to provide ideas for the pathogenesis of osteoarthritis and provide a new theoretical basis for the treatment of osteoarthritis. METHODS: PubMed, Web of Science, Embase, CNKI, VIP, and WanFang databases were used for a literature search for articles published from inception to 2023 concerning the influence of mechanical stress on osteoarthritis and mechanical stress, Hippo pathway, and osteoarthritis. A total of 75 articles were finally reviewed. RESULTS AND CONCLUSION: (1) Different mechanical stresses may play different roles in cell proliferation, apoptosis and differentiation, osteoarthritis inflammation, and vascular homeostasis in osteoarthritis. (2) Hard extracellular matrix, low cell density, medium shear force, medium tensile force, and compression force can achieve cell proliferation, osteogenic differentiation, and vascular homeostasis, and inhibit inflammatory response by activating YAP/TAZ. (3) Soft extracellular matrix, high cell density, excessive shear force, excessive tensile force, and compressive force inhibit cell proliferation, enhance cartilage differentiation, disrupt vascular homeostasis, and promote inflammation through inactivation of YAP/TAZ, thus promoting the process of osteoarthritis. [ABSTRACT FROM AUTHOR]

The aberrant activation of yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), downstream effectors of the Hippo signaling pathway, has been implicated in hepatocellular carcinoma(HCC). The microRNAs (miRNAs) works as a tumor suppressors that influence the proliferation, migration and apoptosis of tumor cells by modulating Hippo-YAP/TAZ signaling during hepatic tumorigenesis. Exploring the role of miRNAs in regulating Hippo YAP/TAZ pathway in HCC can provide new ideas for the diagnosis and treatment of HCC.

The aberrant activation of yes-associated protein（YAP） and transcriptional coactivator with PDZ-binding motif（TAZ）, downstream effectors of the Hippo signaling pathway, has been implicated in hepatocellular carcinoma（HCC）. The microRNAs（miRNAs） works as a tumor suppressors that influence the proliferation, migration and apoptosis of tumor cells by modulating Hippo-YAP/TAZ signaling during hepatic tumorigenesis. Exploring the role of miRNAs in regulating Hippo YAP/TAZ pathway in HCC can provide new ideas for the diagnosis and treatment of HCC. [ABSTRACT FROM AUTHOR]

Objective: To explore the mechanism of aspirin inhibiting intracranial aneurysm formation in rats by regulating Hippo pathway. Methods: Forty healthy SD rats were selected and divided into control group (without any treatment), sham operation group (exposing the posterior branches of bilateral renal arteries and left common carotid artery, but without ligation), aneurysm group (perfusing normal saline after ligating the posterior branches of bilateral renal arteries and left common carotid artery) and aspirin group (perfusing aspirin after artery ligation), with 10 rats in each group. Detection of serum inflammatory factors [tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), IL-10)] and vascular endothelial injury markers [nitric oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)] 12 weeks after intragastric administration. After the rats were killed, the aneurysm size, wall thickness ratio, lumen area and thinning length of the middle membrane were detected. The expression of Yes-associated protein (YAP) was detected. Results: 1) There were obvious bulges on the Willis ring in the aneurysm group and aspirin group, and the bulges in the aspirin group were smaller than those in the aneurysm group. The aneurysm size, lumen area and thinning length of middle membrane in aspirin group were smaller than those in aneurysm group, and the wall thickness ratio was greater than that in aneurysm group (P<0.05). (2) The serum levels of TNF-α, MCP-1 and IL-6 of rats in aneurysm group and aspirin group were higher than those in the control group and sham operation group, while the levels of IL-10 were lower than those in the control group and sham operation group (P<0.05); The serum levels of TNF-α, MCP-1 and IL-6 of rats in aspirin group were lower than those in aneurysm group, while the levels of IL-10 were higher than those in aneurysm group (P<0.05). (3) The levels of serum NO, ET-1 and VEGF in aneurysm group and aspirin group were lower than those in control group and sham operation group (P<0.05); The level of serum NO in aspirin group was higher than that in aneurysm group, and the levels of ET-1 and VEGF were higher than that in aneurysm group (P<0.05). (4) The relative absorbance value of YAP protein expression in aneurysm group and aspirin group was significantly higher than that in control group and sham operation group (P<0.05). The relative light absorption value of YAP protein expression in aspirin group was lower than that in aneurysm group (P<0.05). Conclusion: Aspirin can significantly reduce the inflammatory reaction of rats with intracranial aneurysms, improve vascular endothelial function, and inhibit the formation of intracranial aneurysms, which may be related to the regulation of Hippo signal pathway by inhibiting YAP. [ABSTRACT FROM AUTHOR]

Various etiologies cause the destruction of liver microenvironment, which leads to the loss of liver structure and function and initi-ates the process of liver fibrosis. Hepatic stellate cells ( HSCs) are mainly activated into myofibroblasts that secrete a large amount of extra-cellular matrix ( ECM), mostly collagen. Although there have been many studies on the anti - liver fibrosis mechanism, there is still a lack of effective target drugs for clinical application, and in recent years, studies on anti - liver fibrosis have mainly focused on interventions for the advanced stage of liver fibrosis, while ignoring the specific mechanism of early - stage liver fibrosis. Recently, there have been an in-creasing number of studies on Hippo signaling in liver fibrosis, with a focus on the expression of the core transcription factor Yes - associated protein ( YAP) in early activated HSCs and the regulation of HSC status by this pathway. This article mainly introduces the role of the Hippo/YAP pathway in the regulation of early - stage or advanced liver fibrosis and briefly describes the potential role of regulating the stable expression and nuclear translocation of the core transcription factor YAP in reversing liver fibrosis, suggesting that this pathway can provide new directions and targets for clinical treatment. [ABSTRACT FROM AUTHOR]

Objective To understand the expression of YAP factor and macrophage polarization phenotypes M1 and M2 in keloid and to explore the correlation between YAP factor of Hippo pathway and macrophage polarization. Methods From July 2020 to April 2021, TMT proteomic assay was performed on keloid, normal scar and normal skin of 3 patients to screen meaningful cell signaling pathways. The tissue microarrays of 56 keloid tissues, 5 normal skin tissues and 4 normal scar tissues were made for immunofluorescence staining of YAP factors. The differential expression of screened cellular pathway proteins, and double antibody immunofluorescence staining of CD68+iNOS and CD68+CD163, the surface markers of macrophages M1 and M2 were verified. The correlation was analyzed. Results TMT proteomics screening showed that Hippo signaling pathway was differentially expressed in keloid, and YAP factor expression was elevated in keloid compared with normal skin, and fibroblast YAP cell nuclear expression was increased compared with normal skin and normal scar. Macrophage M1 and M2 were elevated in keloid and normal scar compared with normal skin, with M2 predominantly elevated. The M2/M1 ratio showed significant elevation in keloid compared with normal scar and normal skin. In addition, the M2/M1 ratio was significantly correlated with YAP nuclear expression. Conclusion The formation of keloid is correlated with macrophage polarization and expression of YAP factor. Macrophage polarization toward M2 may promote keloid formation through abnormal nuclear expression of YAP factor. [ABSTRACT FROM AUTHOR]

Hippo pathway is highly evolutionarily conserved and is associated with the development and advances of various human diseases.In recent years，studies have shed light on the significant role of Hippo pathway in kidney injury and repair.Some data point out the Hippo pathway loss promotes proliferation and regeneration of tubular epithelial cells after acute kidney injury（AKI）.However，other evidence shows that the persistent inactivation of Hippo pathway in the post-acute phase of AKI may induce the transition of AKI to chronic kidney disease （CKD）. Therefore，a comprehensive understanding of the functional contribution of Hippo pathway in the repair of AKI and the development of CKD will help to discover new therapeutic targets and strategies for AKI. In this review，we summarize how Hippo pathway regulates adaptive repair after AKI and discuss how sustained inactivation of Hippo pathway triggers maladaptive responses and causes CKD progression. [ABSTRACT FROM AUTHOR]

The incidence rate of primary liver cancer continues to increase around the world, with a younger age of onset and poorer prognosis. As the most classic regulator of cell polarity and density, mechanical signal transduction, cell proliferation, and organ development, the Hippo pathway can promote the development and progression of various cancers including primary liver cancer. YAP, a classic nuclear effector of the Hippo pathway, is significantly upregulated in primary liver cancer and promotes the development of drug resistance. This article aims to investigate the association of the dysregulation of the Hippo signaling pathway with the development and progression of primary liver cancer and analyzes the mechanism of action of the Hippo signaling pathway in the drug resistance of primary liver cancer as an early event of the development of primary liver cancer, which is of great significance for exploring new treatment strategies for primary liver cancer. [ABSTRACT FROM AUTHOR]

Objective To explore the effect and mechanism of Yes-associated protein (YAP) in hepatic ischemiareperfusion injury (IRI) of mice. Methods Forty male C57BL/6 mice were randomly divided into the sham operation group (Sham group), lysophosphatidic acid (LPA) + Sham group, IRI group and LPA+IRI group, 10 mice in each group. Liver tissue and serum samples were collected at 6 h after ischemia-reperfusion. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Histopathological changes and macrophage infiltration of liver tissues were detected by hematoxylin-eosin (HE) staining and immunohistochemical staining. The protein expression level of YAP was detected by Western blot. The messenger ribonucleic acid (mRNA) expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), interleukin (IL)-1 and IL-6 were quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). Results Western blot results demonstrated that the protein expression level of YAP in the LPA+IRI group was significantly upregulated than that in the IRI group. Compared with the Sham group, the ALT and AST were significantly higher in the IRI group (both P<0.05). The serum levels of ALT and AST in the LPA+IRI group were significantly lower than those in the IRI group (both P<0.05). HE staining revealed that the morphology of hepatocytes was normal in the Sham group and LPA + Sham group. Pathological changes, such as liver congestion, liver cell swelling and structural abnormalities of hepatic lobule, occurred in the LPA+IRI group and IRI group. Compared with the IRI group, pathological changes were alleviated in the LPA+IRI group. RT-PCR indicated that the mRNA expression levels of TNF-α, iNOS, IL-1 and IL-6 in the LPA+IRI group were lower than those in the IRI group (all P<0.05). Immunohistochemical demonstrated that LPA partially inhibited macrophage infiltration in ischemic tissues after IRI. Conclusions YAP can significantly mitigate hepatic IRI. The mechanism is associated with the regulation of macrophage recruitment and activation. [ABSTRACT FROM AUTHOR]

Objective To explore whether Eya3 protein(Eyes absent homolog 3) affects the chemoresistance of glioma cells by regulating the Hippo pathway. Methods Immunohistochemistry and Western blotting were used to detect the expression of Eya3 in glioma tissues and cell lines. The effect of overexpression or silencing of Eya3 on chemotherapy resistance of U87 cells was detected by MTT assay. The effects of over-expression or silencing of Eya3 on the stemness and migration/invasion ability of U87 cells were examined by three-dimensional balling and migration/invasion experiments, respectively. The effect of Eya3 on the phosphorylation of Hippo pathway was detected by Western blotting. The transcription levels of Sox 2 and Slug genes were detected by ChIP(chromatin immunoprecipitation assay) assay. Results Eya3 was highly expressed in glioma tissues and cells. After overexpression of Eya3, the resistance, stemness, migration and invasion ability of U87 cells increased significantly, while silencing of Eya3 was the opposite. Eya3 inhibits the phosphorylation of Hippo pathway and promotes the nuclear translocation of YAP. The increased YAP enhances the transcription of Sox2 and Slug genes. Conclusion Eya3 affects chemoresistance of glioma cells by regulating the activity of Hippo pathway. [ABSTRACT FROM AUTHOR]

[Objectives] This study was conducted to elucidate the growth performance,the expression levels of Hippo signaling pathway components and AMP-activated protein kinase(AMPK)in the liver of Hu sheep under caloric restriction and compensation situations.[Methods] Thirty-two ram lambs were randomly assigned into control group and compensation growth group(three months of age,n=16)based on the body weight. Caloric restriction period(60 d)and caloric compensation period(90 d)were designed. At caloric restriction period,the animals in the control and the caloric restriction group were fed with normal diet(11.64 MJ·kg-1)and calorie restriction diet(6.84 MJ·kg-1),respectively. Subsequently,at caloric compensation period,animals in both groups were fed with regular diet(12.86 MJ·kg-1)for additional three months. Lambs were slaughtered at the end of caloric restriction and compensation period,the body weights were measured and the liver tissues were collected which were used to analyze the expressions of Hippo signaling pathway components and AMPK by real-time PCR and Western blot.[Results] During the caloric restriction period,the body and liver weights of the lamps significantly decreased in the caloric restriction group(P<0.05). The expression levels of Hippo pathway components,and the translation levels of YAP1 were significantly reduced in the caloric restriction group than those in the control group(P<0.05),while the mRNA level of AMPK and protein level of pAMPK significantly increased under caloric restriction(P<0.05). After the caloric re-alimentation,no significant differences in growth or tested hepatic elements were detected.[Conclusions] The Hippo pathway and AMPK in liver tissues might effectively participate in the metabolic regulation under temporal energy restriction and subsequent re-alimentation. [ABSTRACT FROM AUTHOR]

Objective To study the protein level, subcellular localization of the hippo pathway core molecules Yap (Yes-associated protein) / Transcriptional co-activator with PDZ-binding motif (Taz) in human gliomas. Methods The protein levels of Yap/Taz in the nontumorous brain tissues and glioma samples were examined by Western blot (WB) and immunohistochemical staining (IHC). Results The levels of Yap / Taz were up-regulated in glioma tissues and mainly located in the nucleus. In addition, the protein levels of Yap / Taz were increased with the glioma grade increased. Conclusion Yap / Taz are highly expressed in human brain glioma samples, indicating that Yap / Taz are involved in glioma progression. [ABSTRACT FROM AUTHOR]

Objective: To investigate the phosphorylation levels of Hippo pathway proteins in thrombin stimulated platelets and to explore its effects on platelet activation., Methods: The phosphorylation levels of Hippo pathway proteins - Mammalian STE20-like kinase 1/2 (MST1/2), Nuclear Dbf2 related kinase 1/2 (NDR1/2) and Mps one binder 1(MOB1) in human thrombin stimulated platelets was detected by Western blot. The effect of MST1/2 inhibitor XMU-MP-1 on platelet aggregation was detected by Platelet Aggregometer. The effect of XMU-MP-1 on platelet integrin αIIbβ3 activation and CD62p expression was detected by flow cytometry. The effect of XMU-MP-1 on the "outside-in" signal of platelet integrin was detected by blood clot retraction test. The effects of XMU-MP-1 on platelet Hippo pathway proteins and p38 phosphorylation levels was detected by Western blot., Results: The phosphorylation levels of MST1/2, NDR1/2 and MOB1 were significantly increased in thrombin activated platelets; XMU-MP-1 inhibited thrombin-induced platelet aggregation and αIIbβ3 activation, but did not affect α-granules release and clot retraction. In addition, thrombin induced phosphorylation of the Hippo proteins were decreased in XMU-MP-1 treated platelets, while the phosphorylation of p38 was not affected., Conclusion: In thrombin stimulated platelets, Hippo pathway proteins were activated and contributed to platelets activation.