Based on previous research, it's unclear about the signaling pathway involved in the negative regulation of T-lymphocyte proliferation in thymus by monochromatic red light. Newly hatched chicks were randomly assigned divided into white (WL), red (RL), green (GL), and blue (BL) light treatments. Three days later, each light treatment group was further divided into intact, sham operation, and pinealectomy groups. The findings revealed that RL led to an increase in the expression of RORα and RORγ, while p-AKT/p-GSK3β/β-catenin/CyclinD1 expression in the thymus of chicks were decreased. Conversely, GL showed opposite results compared to RL. After pinealectomy, accompanied with the expression of RORα and RORγ increased under four light, p-AKT/ p-GSK3β/ β-catenin/ CyclinD1 expression were decreased. In vitro, exogenous melatonin increased the p-AKT/β-catenin/CyclinD1 expression in the thymic lymphocytes of chick reared under RL. The stimulative effect of melatonin was enhanced by SR3335 (RORα antagonist) or GSK298 (RORγ antagonist), while it was attenuated by SR1078 (RORα/RORγ agonist), LY-294 (PI3K antagonist) and HY-102 (AKT antagonist). These results demonstrate that RORα/RORγ negatively regulate monochromatic red light induced-T-lymphocyte proliferation in the thymus, possibly through the PI3K/AKT/p-GSK3β (Ser9) signaling pathway.

2024-11-01·Biochemical and Biophysical Research Communications

Retinoic acid receptor-related orphan receptor alpha and synthetic RORα agonist against invasion and metastasis in tongue squamous cell carcinoma

Article

作者: Zeng, Ran ; Wang, Mohan ; Zheng, Shuang ; Qian, Yong

Retinoic acid receptor-related orphan receptor alpha (RORα), an essential tumor suppressor in a range of human malignancies, is classified as a member of the orphan nuclear receptor family. The most prevalent form of oral cancer, tongue squamous cell carcinoma (TSCC) is characterized by its severe malignancy and unfavorable prognosis. However, the extent to which its tumorigenesis mechanisms are associated with RORα expression levels is still not fully understood. The objective of this study was to examine the molecular mechanisms by which RORα is involved in TSCC. Through the use of immunohistochemistry (IHC), it was discovered that the expression level of RORα was significantly downregulated in TSCC tissues when compared to adjacent normal tissues in this study. To further investigate the role of RORα in TSCC, we activated the expression of RORα in human TSCC cell line (SCC9 cells) by transfecting RORα cDNA and using the selective RORα agonist SR1078. The results show that RORα can significantly inhibit the invasion, migration, proliferation, and adhesion of TSCC cells and induce cell apoptosis. In addition, xenograft models confirmed the conclusion that stable activation or treatment with SR1078 to increase RORα content significantly inhibited tumor growth and development. Taken together, this study provides solid evidence for the inhibitory role of RORα in the progression of TSCC. In addition, the preliminary application results of SR1078 in TSCC show that SR1078 is expected to be a potential therapeutic medication for TSCC. These findings provide innovative perspectives on the development of potential biomarkers and agents for TSCC therapy. The objective is to introduce novel strategy and alternatives for the prevention and treatment of TSCC.

2024-10-01·Ecotoxicology and Environmental Safety

Exosomal miR-205–5p contributes to the immune liver injury induced by trichloroethylene: Pivotal role of RORα mediating M1 Kupffer cell polarization

Article

作者: Wang, Hui ; Zhou, Pengcheng ; Wu, Changhao ; Li, Yu ; Cai, Shuyang ; Wu, Qifeng ; Zhu, Qixing ; Wang, Feng ; Ding, Tao

Trichloroethylene (TCE) is a common environmental contaminant that can induce occupational dermatitis medicamentosa-like TCE (ODMLT), where the liver damage is the most common complication. The study aims to uncover the underlying mechanism of TCE-sensitization-induced liver damage by targeting specific exosomal microRNAs (miRNAs). Among the enriched serum exosomal miRNAs of ODMLT patients, miR-205-5p had a significant correlation coefficient with the liver function damage indicators. Moreover, retinoic acid receptor-related orphan receptor α (RORα) was identified as a direct target of miR-205-5p via specific binding. Further experiments showed that kupffer cells (KCs) underwent M1 phenotypic and functional changes in liver injury induced by TCE which were alleviated by reducing the expression of miR-205-5p. However, this alleviation was reversed by the RORα antagonist SR1001. In vitro experiments showed that miR-205-5p promoted M1 polarization of macrophages and enhanced the secretion of inflammatory factors by regulating RORα. An increase in RORα reversed the polarization direction of M1-type macrophages and reduced the secretion of proinflammatory factors. In addition, pretreatment of mice with SR1078, a specific RORα agonist, effectively blocked M1 polarization of KCs and reduced the severity of TCE-induced liver injury. Our study uncovers that miR-205-5p regulates KC M1 polarization by targeting RORα in immune liver injury induced by TCE sensitization, providing new insight into the molecular mechanisms and new therapeutic targets for ODMLT.

100 项与 SR-1078 相关的药物交易

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