摘要:
Transcription factors, as the convergence points of multiple signaling pathways in eukaryotic cells, are closely involved in disease development. Pax-8, an important transcription factor belonging to the Pax family, exerts a crucial influence on the regulation of gene expression required for both physiological conditions and pathological processes. Pax-8 contributes to the pathogenesis of many human diseases, ranging from cardiovascular disease to many cancers, and therefore, it can be imagined that Pax-8 holds great therapeutic potential. In this review, we summarize the structure, distribution, function, and regulatory mechanisms of Pax-8 to provide a new research direction for Pax-8. 1. Pax-8, as an important transcription factor, has been described as a distinct temporal and spatial expression pattern and tissue-specific manner during growth and differentiation in the developing embryo. 2. The up-regulation or down-regulation of Pax-8 is involved in many pathological processes, including cell apoptosis, ventricular septum defect formation, adipocyte-like cell differentiation, angiogenesis, and tumor progression. 3. PPFP is a Pax-8-PPAR gamma fusion protein produced by a specific gene fusion, participating in adipocyte-like cell differentiation and tumor progression. 4. Pax-8 may be an attractive therapeutic target for atherosclerotic diseases.image
作者:
Yang Wu-Zhou;Li Heng;Yu Xiao-Hua;Zhang Jie;Huang Xin-Yun;...
期刊:
生物化学与生物物理进展,2022年49(2):401-412 ISSN:1000-3282
通讯作者:
Cao Qi;Tang, CK
作者机构:
[Li Heng; Cao Qi; Yang Wu-Zhou; Zhao Zhen-Wang; Zhang Jie; Tang Chao-Ke; Huang Xin-Yun] Univ South China, Key Lab Arteriosclerol Hunan Prov, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Affiliated Hosp 2,Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.;[Yu Xiao-Hua] Hainan Med Univ, Inst Clin Med, Affiliated Hosp 2, Haikou 460106, Peoples R China.
通讯机构:
[Cao, Q; Tang, CK ] U;Univ South China, Key Lab Arteriosclerol Hunan Prov, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Affiliated Hosp 2,Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.
关键词:
miR-216b;ABCG1
摘要:
Objective To investigated the function and the target gene of miR-216b in osteoclast differentiation and explored its effect on osteoclast cholesterol efflux.Methods The cell model of RAW264.7 osteoclast precursor cell differentiation induced by RANKL stimulation was established.Tartrate-resistant acid phosphatase(TRAP)staining assay was conducted to evaluate osteoclasts differentiation.MiR-216b target gene,ABCG1 3' untranslated region(3'UTR)sequence and free energy were predicted and analyzed by bioinformatics analyses and dual-luciferase reporter assays.MiR-216b mimic or inhibitor transfection was performed to verify the role of miR-216b in osteoclast differentiation.Liquid scintillation counting was used to measure [3H]-labeled cholesterol efflux from RAW264.7 macrophage-derived osteoclasts.The lipid accumulation in RAW264.7 macrophages was detected by high performance liquid chromatography(HPLC).Real-time quantitative PCR(RT-qPCR)and Western blot assays were used to assess the transcriptional and post-transcriptional levels of ABCG1 in osteoclasts.Results Our results showed that the number of osteoclasts,the average diameter of osteoclasts and the fusion index were significantly increased when cells were transfected with miR-216b mimic,as revealed by tartrate-resistant acid phosphatase-positive staining and microscopy assay.MiR-216b inhibitor showed the complete opposite outcome which brought additional evidence to our findings.Bioinformatics analysis and dualluciferase reporter assays showed that miR-216b targets the 3'UTR of ABCG1.Moreover,miR-216b suppressed both the mRNA and protein levels of ABCG1 in osteoclasts.Besides,we found that silencing of ABCG1 by ABCG1 siRNA increased the number of osteoclasts,the average diameter of osteoclasts and the fusion index.MiR-216b reduced cholesterol efflux from osteoclasts by inhibiting ABCG1 expression.Conclusion Collectively,these findings suggest that miR-216b downregulates ABCG1 expression and inhibits osteoclast cholesterol efflux,which disturbs cholesterol homeostasis and promotes osteoclastogenesis.
摘要:
高甘油三酯血症与肥胖和2型糖尿病紧密相关。肥胖和2型糖尿病常伴随胰岛素抵抗,说明胰岛素抵抗可能是影响高甘油三酯血症的重要因素。胰岛素能够抑制叉头盒O1(Forkhead box protein O1,FOXO1)表达;而胰岛素抵抗状态下,FOXO1活性增加,且引起高甘油三酯血症。因此,本文将综述FOXO1在糖代谢和脂代谢及高甘油三酯血症中的作用,为治疗肥胖症和2型糖尿病患者的高甘油三酯血症提供新思路。
摘要:
Myristica fragrans is a traditional herbal medicine and has been shown to alleviate the development of atherosclerosis. However, the anti-atherogenic mechanisms of M. fragrans are still to be addressed. In this study, we explored the effect of M. fragrans on lipid metabolism and inflammation and its mechanisms in THP-1-derived macrophages. The quantitative polymerase chain reaction and western blot analysis results showed that M. fragrans promotes cholesterol efflux from THP-1-derived macrophages and reduces intracellular total cholesterol, cholesterol ester, and free cholesterol contents in a dose- and a time-dependent manner. Further study found that liver X receptor alpha (LXRα) antagonist GGPP significantly blocked the upregulation of ABCA1 expression with M. fragrans treatment. In addition, chromatin immunoprecipitation assay confirmed that GATA binding protein 3 (GATA3) can bind to the LXRα promoter, and inhibition of GATA3 led to the downregulation of LXRα and ATP-binding cassette subfamily A member 1 expression. Furthermore, M. fragrans reduced lipid accumulation, followed by decreasing tumor necrosis factor-α, interleukin (IL)-6, and IL-1β and increasing IL-10 produced by THP-1-derived macrophages. Therefore, M. fragrans is identified as a valuable therapeutic medicine for atherosclerotic cardiovascular disease.
摘要:
Interleukin-5 (IL-5) is manifested as its involvement in the process of atherosclerosis, but the mechanism is still unknown. In this study, we explored the effect of IL-5 on lipid metabolism and its underlying mechanisms in THP-1-derived macrophages. The quantitative polymerase chain reaction (qPCR) and western blot analysis results showed that IL-5 significantly up-regulated ATP-binding cassette transporter A1 (ABCA1) expression in a dose-dependent and time-dependent manner. [3H]-labeled cholesterol was used to assess the levels of cholesterol efflux, and the results showed that IL-5 increased ABCA1-mediated cholesterol efflux. A high-performance liquid chromatography assay indicated that cellular cholesterol content was decreased by IL-5 treatment in THP-1-derived macrophages. The selective inhibitor and small interfering RNA were used to block the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway. The results of the qPCR and western blot analysis showed that IL-5 activated JAK2/STAT3 pathway to up-regulate ABCA1 expression. Meanwhile, IL-5 reduced the expression level of miR-211. Furthermore, we found that JAK2 is a target gene of miR-211 and miR-211 mimic inhibited the expression of JAK2 and reduced the levels of p-STAT3 and ABCA1 as revealed by luciferase reporter assay, qPCR and western blot analysis. In summary, these findings indicated that IL-5 promotes ABCA1 expression and cholesterol efflux through the miR-211/JAK2/STAT3 signaling pathway in THP-1-derived macrophages.
摘要:
Atherosclerosis is regarded as a lipid-driven chronic inflammatory disease. A variety of immune cells, including B1 cells, play an important role in the occurrence and development of atherosclerosis. T15/E06 is an IgM Nab secreted by B1 cells. The concentration of T15/E06 is significantly decreased in animal models of atherosclerosis. Accumulating evidence has shown that T15/E06 can protect against atherosclerosis by blocking macrophage lipid uptake, inhibiting vascular inflammation, and promoting apoptotic cell clearance. In this review, we describe the structure, functions and regulation of T15/E06 and summarize the latest advance regarding its atheroprotective effect.