Yes-Associated Protein 1: Role and Treatment Prospects in Orthopedic Degenerative Diseases

Xie, Wenqing; Xiao, Wenfeng; Tang, Kun; Zhang, Jintao; Li, Yusheng

doi:10.3389/fcell.2020.573455

Cited by 15 publications

(13 citation statements)

References 118 publications

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“…Yes-associated protein (YAP) is the final effector of the Hippo signaling pathway, which plays an important role in organ morphogenesis, cell proliferation and differentiation, and tissue homeostasis and regeneration [26]. Recently, several studies have shown that Hippo/YAP signaling may play a predominant role in the pathogenesis of orthopedic degenerative diseases, such as osteoarthritis and osteoporosis [27]. A study by Deng et al [28] showed that YAP activation can protect articular cartilage and YAP depletion in chondrocytes may increase cartilage destruction.…”

Section: Introductionmentioning

confidence: 99%

Melatonin reverses tumor necrosis factor-alpha-induced metabolic disturbance of human nucleus pulposus cells via MTNR1B/Gαi2/YAP signaling

Qiu¹,

Liang²,

Wu³

et al. 2022

Int. J. Biol. Sci.

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Background: Intervertebral disc degeneration (IDD), the main cause of low back pain, is closely related to the inflammatory microenvironment in the nucleus pulposus (NP). Tumor necrosis factor-α (TNF-α) plays an important role in inflammation-related metabolic disturbance of NP cells. Melatonin has been proven to regulate the metabolism of NP cells, but whether it can protect NP cells from TNF-α-induced damage is still unclear. Therefore, this study aims to investigate the role and specific mechanism of melatonin on regulating the metabolism of NP cells in the inflammatory microenvironment. Methods: Western blotting, RT-qPCR and immunohistochemistry were used to detect the expression of melatonin membrane receptors (MTNR1A/B) and TNF-α in human NP tissues. In vitro, human primary NP cells were treated with or without vehicle, TNF-α and melatonin. And the metabolic markers were also detected by western blotting and RT-qPCR. The activity of NF-κB signaling and Hippo/YAP signaling were assessed by western blotting and immunofluorescence. Membrane receptors inhibitors, pathway inhibitors, lentiviral infection, plasmids transfection and immunoprecipitation were used to explore the specific mechanism of melatonin. In vivo, the rat IDD model was constructed and melatonin was injected intraperitoneally to evaluate its therapeutical effect on IDD. Results:The upregulation of TNF-α and downregulation of melatonin membrane receptors (MTNR1A/B) were observed in degenerative NP tissues. Then we demonstrated that melatonin could alleviate the development of IDD in a rat model and reverse TNF-α-impaired metabolism of NP cells in vitro. Further investigation revealed that the protective effects of melatonin on NP cells mainly rely on MTNR1B, which subsequently activates Gαi2 protein. The activation of Gαi2 could upregulate the yes-associated protein (YAP) level, resulting in anabolic enhancement of NP cells. In addition, melatonin-mediated YAP upregulation increased the expression of IκBα and suppressed the TNF-αinduced activation of the NF-κB pathway, thereby inhibiting the catabolism of NP cells. Conclusions:Our results revealed that melatonin can reverse TNF-α-impaired metabolism of NP cells via the MTNR1B/Gαi2/YAP axis and suggested that melatonin can be used as a potential therapeutic drug in the treatment of IDD.

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Section: Introductionmentioning

confidence: 99%

Melatonin reverses tumor necrosis factor-alpha-induced metabolic disturbance of human nucleus pulposus cells via MTNR1B/Gαi2/YAP signaling

Qiu¹,

Liang²,

Wu³

et al. 2022

Int. J. Biol. Sci.

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“…4 ). Yap1 is a key downstream effector of the Hippo pathway ( Xie et al, 2020 ). The Hippo signaling pathway has been found to mediate chondrocyte differentiation and postnatal growth ( Roselló-Díez & Joyner, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Transcription analyses of differentially expressed mRNAs, lncRNAs, circRNAs, and miRNAs in the growth plate of rats with glucocorticoid-induced growth retardation

Yin

Wang

Zhang

et al. 2023

PeerJ

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Background Glucocorticoids (GCs) are commonly used to treat autoimmune diseases and malignancies in children and adolescents. Growth retardation is a common adverse effect of GC treatment in pediatric patients. Accumulating evidence indicates that non-coding RNAs (ncRNAs) are involved in the pathogenesis of glucocorticoid-induced growth retardation (GIGR), but the roles of specific ncRNAs in growth remain largely unknown. Methods In this study, 2-week-old male Sprague-Dawley rats had been treated with 2 mg/kg/d of dexamethasone for 7 or 14 days, after which the growth plate tissues were collected for high-throughput RNA sequencing to identify differentially expressed mRNAs, lncRNAs, circRNAs, and miRNAs in GIGR rats. Results Transcriptomic analysis identified 1,718 mRNAs, 896 lncRNAs, 60 circRNAs, and 72 miRNAs with different expression levels in the 7d group. In the 14d group, 1,515 mRNAs, 880 lncRNAs, 46 circRNAs, and 55 miRNAs with differential expression were identified. Four mRNAs and four miRNAs that may be closely associated with the development of GIGR were further validated by real-time quantitative fluorescence PCR. Function enrichment analysis indicated that the PI3K-Akt signaling pathway, NF-kappa B signaling pathway, and TGF-β signaling pathway participated in the development of the GIGR. Moreover, the constructed ceRNA networks suggested that several miRNAs (including miR-140-3p and miR-127-3p) might play an important role in the pathogenesis of GIGR. Conclusions These results provide new insights and important clues for exploring the molecular mechanisms underlying GIGR.

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“…The Hippo pathway could integrate a lot of signals to directly or indirectly regulate multiple cancer hallmarks, including proliferation, invasion and metastasis, survival, angiogenesis, evading growth suppressors, as well as inflammation and immunosuppression [40,41]. For example, the Hippo pathway could regulate the proliferation through PTEN/AKT/mTOR-mediated autophagy in HCC [42].…”

Section: Discussionmentioning

confidence: 99%

Integrative bioinformatics and experimental analysis revealed TEAD as novel prognostic target for hepatocellular carcinoma and its roles in ferroptosis regulation

Ren

Wang

Yan

et al. 2022

Aging

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Objective: Transcriptional enhanced associate domain (TEAD) family consists of four members TEAD1/2/3/4 that regulate cell growth, stem cell functions and organ development. As the downstream of Hippo signaling pathway, TEAD family is involved in the progression of several cancers. However, the precise biology functions of TEAD family in hepatocellular carcinoma (HCC) have not been reported yet. Methods: We apply bioinformatics analysis based on databases including UALCAN, Oncomine, GEPIA, Kaplan-Meier plotter, WebGestalt, cBioPortal, TIMER2.0, and in vitro experimental evidence to identify the exact roles of TEAD family in HCC. Results: The results indicated that TEAD2/4 were significantly upregulated in HCC compared with normal tissues. Downregulated of TEAD2 could promote the death of HCC cells through inducing ferroptosis by iron accumulation and subsequent oxidative damage. According to the Kaplan-Meier plotter database, we found that the high expression of TEAD2 was significantly associated with poor disease-specific survival, overall survival, progression-free survival and relapse-free survival. In aspect of cancer immunity, Tumor Immune Estimation Resource algorithm showed that the expression of TEAD family members was obviously related to multiple of infiltrating immune cells including macrophages, neutrophils, dendritic cells, B cells, CD8+ T cells and CD4+ T cells. Finally, we conducted the functional enrichment analysis including protein-protein interaction

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Yes-Associated Protein 1: Role and Treatment Prospects in Orthopedic Degenerative Diseases

Cited by 15 publications

References 118 publications

Melatonin reverses tumor necrosis factor-alpha-induced metabolic disturbance of human nucleus pulposus cells via MTNR1B/Gαi2/YAP signaling

Melatonin reverses tumor necrosis factor-alpha-induced metabolic disturbance of human nucleus pulposus cells via MTNR1B/Gαi2/YAP signaling

Transcription analyses of differentially expressed mRNAs, lncRNAs, circRNAs, and miRNAs in the growth plate of rats with glucocorticoid-induced growth retardation

Integrative bioinformatics and experimental analysis revealed TEAD as novel prognostic target for hepatocellular carcinoma and its roles in ferroptosis regulation

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