期刊:
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids,2021年1866(5):158904- ISSN:1388-1981
通讯作者:
Yu, Xiao-Hua;Tang, Chao-Ke
作者机构:
[Qin, Yu-Sheng; Tang, Chao-Ke; Liao, Ling-Xiao; Zhao, Zhen-Wang; Zhou, Li; Li, Heng; Wang, Gang; Zou, Jin; Wan, Xiang-Jun; Zhang, Min] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang Med Sch,Hunan Prov Cooperat Innovat Ctr, Hengyang 421001, Hunan, Peoples R China.;[Liao, Ling-Xiao] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Yu, Xiao-Hua] Hainan Med Univ, Inst Clin Med, Affiliated Hosp 2, Haikou 460106, Hainan, Peoples R China.
通讯机构:
[Yu, Xiao-Hua; Tang, Chao-Ke] I;Institute of Clinical Medicine, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 460106, China. Electronic address:;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic disease, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China. Electronic address:
摘要:
OBJECTIVE: The purpose of this study was to explore the role of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in atherosclerosis and the underlying mechanism. METHODS: The Gene Expression Omnibus (GEO) datasets were used to divide differentially expressed lncRNAs, microRNAs (miRNAs), and mRNAs. The expression of PCA3, miR-140-5p, RFX7 and ABCA1 were determined by qPCR or Western blot in ox-LDL-treated macrophages. Macrophage lipid accumulation s was evaluated using the Oil Red O staining and high-performance liquid chromatography. Target relationships among PCA3, miR-140-5p, RFX7, and ABCA1 promoter area were validated via dual-luciferase reporter gene assay or chromatin immunoprecipitation assay. The apoE(-/-) mouse model in vivo was designed to evaluate the effect of PCA3 on the reverse cholesterol transport (RCT) and atherosclerosis. RESULTS: PCA3 was down-regulated in foam cells, whereas miR-140-5p was highly expressed. Overexpression of PCA3 promoted ABCA1-mediated cholesterol efflux and reduced lipid accumulation in macrophages. Besides, RFX7 bound to the ABCA1 promoter and increased ABCA1 expression. Targeted relationships and interactions on the expression between miR-140-5p and PCA3 or RFX7 were elucidated. PCA3 up-regulated ABCA1 expression by binding to miR-140-5p to up-regulate RFX7 and ABCA1 expression in macrophages. PCA3 promoted RCT and impeded the progression of atherosclerosis by sponging miR-140-5p in apoE(-/-) mice. Meanwhile, miR-140-5p also inhibit ABCA1 expression via downregulation of RFX7 to impede RCT and aggravate atherosclerosis. CONCLUSIONS: lncRNA PCA3 promotes ABCA1-mediated cholesterol efflux to inhibit atherosclerosis through sponging miR-140-5p and up-regulating RFX7.
作者机构:
[Yang, Hui-xian] Univ South China, Med Coll, Inst Cardiovasc Dis, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Liao, Duan-fang; Chen, Jian-xiong; Tuo, Qin-hui] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;[Tian, Ying; Long, Shi-yin; Yang, Hui-xian; Zhang, Cai-ping; Zhang, Min; Liao, DF] Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Jian-xiong] Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, University, MS 38677 USA.
通讯机构:
[Zhang, CP; Liao, DF] U;Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
Dyslipidemia;IDOL;LDL-C;LDLR;PCSK9;SREBP2
摘要:
The SREBP2/LDLR pathway is sensitive to cholesterol content in the endoplasmic reticulum (ER), while membrane low-density lipoprotein receptor (LDLR) is influenced by sterol response element binding protein 2 (SREBP2), pro-protein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL). LDL-C, one of the risk factors in cardiovascular disease, is cleared through endocytosis recycling of LDLR. Therefore, we propose that a balance between LDLR endocytosis recycling and PCSK9-mediated and IDOL-mediated lysosomal LDLR degradation is responsible for cholesterol homeostasis in the ER. For statins that decrease serum LDL-C levels via cholesterol synthesis inhibition, the mechanism by which the statins increase the membrane LDLR may be regulated by cholesterol homeostasis in the ER.
期刊:
International braz j urol,2019年45(2):220-228 ISSN:1677-5538
通讯作者:
Cao, Zhaohui
作者机构:
[Cao, Zhaohui; Hu, Xiaobo] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.;[Hu, Cong; Cao, Zhaohui; Hu, Xiaobo; Long, Shiyin; Zhang, Caiping; Zhang, Min] Univ South China, Sch Pharm & Biosci, Dept Biotechnol, Hengyang, Peoples R China.
通讯机构:
[Cao, Zhaohui] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Peoples R China.
关键词:
ABSTRACT Obesity is defined as a chronic and excessive growth of adipose tissue. It has been associated with a high risk for development and progression of obesity-associated malignancies, while adipokines may mediate this association. Adiponectin is an adipose tissue-derived adipokines, with significant anti-diabetic, anti-inflammatory, anti-atherosclerotic and anti-proliferative properties. Plasma adiponectin levels are decreased in obese individuals, and this feature is closely correlated with development of several metabolic, immunological and neoplastic diseases. Recent studies have shown that prostate cancer patients have lower serum adiponectin levels and decreased expression of adiponectin receptors in tumor tissues, which suggests plasma adiponectin level is a risk factor for prostate cancer. Furthermore, exogenous adiponectin has exhibited therapeutic potential in animal models. In this review, we focus on the potential role of adiponectin and the underlying mechanism of adiponectin in the development and progression of prostate cancer. Exploring the signaling pathways linking adiponectin with tumorigenesis might provide a potential target for therapy. Keywords: Prostatic Neoplasms;Obesity;Stress, Physiological
作者机构:
[Zhang, Mengxia] Hunan Univ Chinese Med, Dept Histol & Embryol, Changsha 410208, Hunan, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.;[Zhang, Mengxia; Liu, Qi; Mo, Zhongcheng] Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.;[Tang, Shengsong; Lei, Xiaoyong; Tu, Jian; Li, Lijun] Univ South China, Insitute Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Ning, Jing; Tang, Shengsong] Hunan Univ Med, Dept Pharmacol, Huaihua 418000, Hunan, Peoples R China.
通讯机构:
[Tang, Shengsong] H;Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.
关键词:
macrophage colony-stimulating factor;breast cancer;apoptosis;HIF-1 and BINP3
摘要:
Macrophage colony-stimulating factor (M-CSF), a tumour marker, is related to tumour cell anti-apoptosis and drug resistance. However, the role of M-CSF in MCF-7 cells is unknown. In the present study, the effect and mechanism of M-CSF on hypoxia-inducible factor-1 (HIF-1)/BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/Apoptosis Regulator BAX signalling in human breast cancer MCF-7 cells were investigated. Western blotting revealed that the expression of HIF-1, BNIP3, Bax, caspase-3 and caspase-9 was lower in MCF-7-M cells compared to MCF-7 and MCF-7-C cells treated with adriamycin (ADM). Immunoprecipitation combined with western blotting was used to detect the interaction between Bcl-2 and BNIP3 or Bax protein. MCF-7-M cells had a higher amount of Bax binding to Bcl-2 compared to MCF-7 cells or MCF-7-C cells, while the amount of BNIP3 binding to Bcl-2 was decreased in MCF-7-M cells. Hoechst 33342 staining and flow cytometry were utilized to evaluate the effect of M-CSF on apoptosis in MCF-7 cells treated with ADM. Compared to ADM-treated MCF-7 cells, the apoptotic rate of MCF-7-M cells was significantly decreased. These effects were dependent on the concentration of ADM. In conclusion, cytoplasmic M-CSF suppressed apoptosis by inhibiting the HIF-1/BNIP3/Bax signalling pathway, which potentiated the dissociation of Bcl-2 from Bcl-2-BNIP3 compounds and the formation of Bcl-2-Bax compounds.
摘要:
BACKGROUND AND AIMS: Kruppel-like factor 14 (KLF14) is known to play a role in atherosclerosis, but the underlying mechanisms are still largely unknown. The aim of our study was to explore the effects of KLF14 on lipid metabolism and inflammatory response, providing a potential target for lowering the risk of atherosclerosis-causing disease. METHODS AND RESULTS: mRNA and protein levels of KLF14 were significantly decreased in oxidized low-density lipoprotein (oxLDL)-treated macrophages and in the atherosclerotic lesion area. Chromatin immunoprecipitation (ChIP) and luciferase reporter gene assays were used to confirm that KLF14 positively regulated miR-27a expression by binding to its promoter. We also found that KLF14 could restored appropriate cellular lipid homeostasis and inflammatory responses via negatively regulating lipoprotein lipase (LPL) expression in THP1-derived macrophages through miR-27a. In addition, gypenosides (GP), a KLF14 activator, delayed the development of atherosclerosis in apolipoprotein E deficient (apoE(-/-)) mice. CONCLUSIONS: KLF14 plays an antiatherogenic role via the miR-27a-dependent down-regulation of LPL and subsequent inhibition of proinflammatory cytokine secretion and lipid accumulation.
作者:
Ye, Qiong;Tian, Guo-Ping;Cheng, Hai-Peng;Zhang, Xin;Ou, Xiang;...
期刊:
Journal of Atherosclerosis and Thrombosis,2018年25(3):244-253 ISSN:1340-3478
通讯作者:
Tang, Chao-Ke
作者机构:
[Zhang, Xin; Gong, Duo; Cheng, Hai-Peng; Ye, Qiong; Xia, Xiao-Dan; Zhang, Min; Tang, Chao-Ke; Zhao, Zhen-Wang; Yu, Xiao-Hua; Li, Liang; Xie, Wei; Huang, Chong; Chen, Ling-Yan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Res Ctr, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan P, Hengyang, Hunan, Peoples R China.;[Tan, Ru-Qi; Ye, Qiong; Tian, Guo-Ping; Yang, Feng-Yun; Pan, Yan-Jun] Univ South China, Affiliated Hosp 2, Dept Cardiovasc Med, Hengyang, Hunan, Peoples R China.;[Ou, Xiang] First Hosp Changsha, Dept Endocrinol, Changsha, Hunan, Peoples R China.;[Zhang, Jie] Univ South China, Affiliated Hosp 2, Dept Spinal Surg, Hengyang, Hunan, Peoples R China.;[Zheng, Xi-Long] Univ Calgary, Hlth Sci Ctr, Libin Cardiovasc Inst Alberta, Cumming Sch Med,Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB, Canada.
通讯机构:
[Tang, Chao-Ke] U;Univ South China, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.
关键词:
MiR-134;ANGPTL4;LPL;Atherosclerosis
摘要:
Aims: Atherosclerosis is the most common cause of cardiovascular disease, such as myocardial infarction and stroke. Previous study revealed that microRNA (miR)-134 promotes lipid accumulation and proinflammatory cytokine secretion through angiopoietin-like 4 (ANGPTL4)/lipid lipoprotein (LPL) signaling in THP-1 macrophages. Methods: ApoE KO male mice on a C57BL/6 background were fed a high-fat/high-cholesterol Western diet, from 8 to 16 weeks of age. Mice were divided into four groups, and received a tail vein injection of miR-134 agomir, miR-134 antagomir, or one of the corresponding controls, respectively, once every 2 weeks after starting the Western diet. After 8 weeks we measured aortic atherosclerosis, LPL Activity, mRNA and protein levels of ANGPTL4 and LPL, LPL/low-density lipoprotein receptor related protein 1 Complex Formation, proinflammatory cytokine secretion and lipid levels. Results: Despite this finding, the influence of miR-134 on atherosclerosis in vivo remains to be determined. Using the well-characterized mouse atherosclerosis model of apolipoprotein E knockout, we found that systemic delivery of miR-134 agomir markedly enhanced the atherosclerotic lesion size, together with a significant increase in proinflammatory cytokine secretion and peritoneal macrophages lipid contents. Moreover, overexpression of miR-134 decreased ANGPTL4 expression but increased LPL expression and activity in both aortic tissues and peritoneal macrophages, which was accompanied by increased formation of LPL/low-density lipoprotein receptor-related protein 1 complexes in peritoneal macrophages. However, an opposite effect was observed in response to miR-134 antagomir. Conclusions: These findings suggest that miR-134 accelerates atherogenesis by promoting lipid accumulation and proinflammatory cytokine secretion via the ANGPTL4/LPL pathway. Therefore, targeting miR-134 may offer a promising strategy for the prevention and treatment of atherosclerotic cardiovascular disease.
摘要:
Background and aims: ApoA-1 binding protein (AIBP) is a secreted protein that interacts with apoA-1 and accelerates cholesterol efflux from cells. We have recently reported that AIBP promotes apoA-1 binding to ABCA1 in the macrophage cell membrane, partially through 115-123 amino acids. However, the effects of AIBP on the development of atherosclerosis in vivo remain unknown. Methods: ApoE(-/-) mice with established atherosclerotic plaques were infected with rAAV-AIBP or rAAV-AIBP(Delta 115- 123), respectively. Results: AIBP-treated mice showed reduction of atherosclerotic lesion formation, increase in circulating HDL levels and enhancement of reverse cholesterol transport to the plasma, liver, and feces. AIBP increased ABCA1 protein levels in aorta and peritoneal macrophages. Furthermore, AIBP could diminish atherosclerotic plaque macrophage content and the expression of chemotaxis-related factors. In addition, AIBP prevented macrophage inflammation by inactivating NF-kappa B and promoted the expression of M2 markers like Mrc-1 and Arg-1. However, lack of 115-123 amino acids of AIBP(Delta 115-123) had no such preventive effects on the progression of atherosclerosis. Conclusions: Our observations demonstrate that AIBP inhibits atherosclerosis progression and suggest that it may be an effective target for prevention of atherosclerosis. (C) 2018 Elsevier B.V. All rights reserved.
摘要:
Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and proinflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly decreased cellular levels of total cholesterol, free cholesterol, and cholesterol ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses. Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3'UTR of LPL. In addition, apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells. Finally, we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKCa. Taken together, our results showed that apelin-13 downregulated the expression of LPL via activating the APJ/PKCa/miR-361 -5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and proinflammatory cytokine secretion. Therefore, our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13, and high-light appelin-13 as a promising therapeutic target in atherosclerosis.
作者机构:
Dept of Genetics, Changde Maternal and Child Health-Care Hospital, Changde, Hunan, 415000, China;[张敏; Yu X.-X.; 田英; Duan U.-R.; 龙石银; 麻燕妮; 张彩平] Dept of Biotechnology, University of South China, Hengyang, Hunan, 421001, China;[刘英] Dept of Medicine, Changde Vocational Technical College, Changde, Hunan, 415000, China;[欧露] Dept of Genetics, Changde Maternal and Child Health-Care Hospital, Changde, Hunan, 415000, China, Dept of Biotechnology, University of South China, Hengyang, Hunan, 421001, China