Browsing by Subject "FOXO1"

Now showing 1 - 4 of 4
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    PGC-1α and FOXO1 mRNA levels and fiber characteristics of the soleus and plantaris muscles in rats after hindlimb unloading
    (F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Suzuki, Hideki; Kouzaki, Mitoki; Takeda, Isao; Ishihara, Akihiko
    Fifteen-week-old rats were subjected to unloading induced by hindlimb suspension for 3 weeks. The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and forkhead box-containing protein O1 (FOXO1) mRNA levels and fiber profiles of the soleus and plantaris muscles in rats subjected to unloading (unloaded group) were determined and compared with those of age-matched control rats (control group). The body weight and both the soleus and plantaris muscle weights were lower in the unloaded group than in the control group. The PGC-1α mRNA was downregulated in the soleus, but not in the plantaris muscle of the unloaded group. The FOXO1 mRNA was upregulated in both the soleus and plantaris muscles of the unloaded group. The oxidative enzyme activity was reduced in the soleus, but not in the plantaris muscle of the unloaded group. The percentage of type I fibers was decreased and the percentages of type IIA and IIC fibers were increased in the soleus muscle of the unloaded group, whereas there was no change in fiber type distribution in the plantaris muscle of the unloaded group. Atrophy of all types of fibers was observed in both the soleus and plantaris muscles of the unloaded group. We conclude that decreased oxidative capacity and fiber atrophy in unloaded skeletal muscles are associated with decreased PGC-1α and increased FOXO1 mRNA levels.
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    UCHL1 enhances TSC1 transcription by stabilizing FOXO1 through deubiquitination in knee osteoarthritis
    (2026) Jiawei Lu; Chonghao Gu; Zikang Xie; Zhongyu Xia; Bingqing Guo; Tao Jiang; Yu Wang; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
    Ferroptosis has been shown to play a significant role in the pathophysiological progression of knee osteoarthritis (KOA). In this study, we sought to investigate the biological role of Ubiquitin C-terminal hydrolase 1 (UCHL1) in KOA and elucidate its underlying molecular mechanisms. An in vitro KOA cell model was established by stimulating C28/I2 chondrocytes with IL-1β, and UCHL1 expression was decreased in IL-1β-treated chondrocytes. Notably, overexpression of UCHL1 significantly alleviated IL-1β induced ferroptosis and extracellular matrix (ECM) degradation. Mechanistically, UCHL1 facilitated the deubiquitination and stabilization of FOXO1. Knockdown of FOXO1 partially reversed the inhibitory effects of UCHL1 on ferroptosis and ECM degradation. Furthermore, FOXO1 was found to bind to the Tuberous Sclerosis Complex 1 (TSC1) promoter, enhancing TSC1 transcription. Intriguingly, knockdown of FOXO1 counteracted the inhibitory effects of UCHL1 overexpression on ferroptosis and ECM degradation, while these effects were rescued by TSC1 overe xpression. In vivo experiments demonstrated that UCHL1 alleviated cartilage damage in KOA rats by inhibiting ferroptosis and ECM degradation through the FOXO1/TSC1 axis. These findings demonstrate the pivotal role of UCHL1 in regulating ferroptosis and maintaining ECM homeostasis, offering novel insights into the molecular mechanisms driving KOA progression.
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    Up-regulation of microRNA-183 reduces FOXO1 expression in gastric cancer patients with Helicobacter pylori infection
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Qi, Chuan; Liu, Li; Wang, Jiayu; Jin, Yu
    The aim of the study is to detect the expression of FOXO1 mRNA and protein in samples from gastric cancer patients with Helicobacter pylori (H. pylori) infection, and to investigate the relationship between FOXO1 expression and miR-183 expression. Twenty-six gastric cancer patients with H. pylori infection and 26 gastric cancer patients without H. pylori infection were included into experimental group and control group, respectively. Tumor tissues and peripheral blood were collected from all subjects. QRT-PCR was used to determine the expression of miRNA and mRNA. Western blotting was carried out to measure protein expression. Dual luciferase reporter assay was used to identify direct interaction between miRNA and 3’-UTR of mRNA. Cell proliferation was examined by CCK-8 assay. FOXO1 mRNA and protein expression was downregulated in gastric cancer patients, being possibly related to H. pylori infection. The expression of miR-183 in tumor tissues and serum from gastric cancer patients with H. pylori infection was elevated, and probably regulated the expression of FOXO1 by direct targeting. Stimulation by H. pylori up-regulated the expression of miR-183 in gastric cancer AGS cells, and reduced the levels of FOXO1 mRNA and protein. Inhibition of miR183 elevated the expression of FOXO1 and suppressed the proliferation of AGS cells. The present study demonstrates that the expression of FOXO1 in tumor tissues and blood from gastric cancer patients with H. pylori infection is significantly down-regulated, and may be related to the up-regulation of miR-183. H. pylori may regulate FOXO1 expression through miR-183 to affect the pathological process of gastric cancer.
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    β-Ecdysone attenuates cartilage damage in a mouse model of collagenase-induced osteoarthritis via mediating FOXO1/ADAMTS-4/5 signaling axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Han, Junzhu; Guan, Jianzhong; Zhu, Xunbing
    Background. β-Ecdysone has been reported to perform a protective effect to prevent interleukin 1β (IL-1β)-induced apoptosis and inflammatory response in chondrocytes. In our study, the chondroprotective effects of β-Ecdysone were explored in a mouse model of collagenase-induced osteoarthritis (OA). Methods. Injection of collagenase in the left knee was implemented to establish a mouse model of OA. The histomorphological analysis was detected using safranine O staining. Serum pro-inflammatory cytokines were measured by ELISA assays. Protein expression in the femur and chondrocytes was analyzed using western blot. Chondrocyte apoptosis was evaluated by terminaldeoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining. Results. Treatment of OA mice with β-Ecdysone supplementation significantly inhibited the production of pro-inflammatory cytokines. Histologic examination exhibited that the degradation of proteoglycans and the loss of trabecular bone were observed in collagenaseinjected mice. However, OA-like changes were attenuated by β-Ecdysone administration in collagenaseinjected mice. Both in vivo and in vitro models, nuclear forkhead box O1 (FOXO1) protein expression was significantly reduced in the femur of collagenase-treated mice and IL-1β-stimulated chondrocytes. However, βEcdysone treatment was able to rescue FOXO1 protein expression in the nucleus to inhibit the transcription and translation of a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 4 (ADAMTS-4) and ADAMTS-5. Conclusion. The findings suggested that β-Ecdysone functioned as a FOXO1 activator to protect collagenaseinduced cartilage damage. FOXO1 might be a potential molecular target of β-Ecdysone for the effective prevention and treatment of OA.