Cellular signalling最新文献_第4页

Corrigendum to “Recent progress of protein kinase inhibitors derived from marine peptides for developing anticancer gents” [Cellular Signalling 124 (2024) 111411] 从海洋肽中提取蛋白激酶抑制剂用于开发抗癌剂的最新进展"[Cellular Signalling 124 (2024) 111411]的更正。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-10 DOI: 10.1016/j.cellsig.2024.111449

引用次数: 0

Fangchinoline inhibits metastasis and reduces inflammation-induced epithelial-mesenchymal transition by targeting the FOXM1-ADAM17 axis in hepatocellular carcinoma 方棘霉素通过靶向 FOXM1-ADAM17 轴抑制肝细胞癌转移并减少炎症诱导的上皮-间质转化

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-10 DOI: 10.1016/j.cellsig.2024.111467

{"title":"Fangchinoline inhibits metastasis and reduces inflammation-induced epithelial-mesenchymal transition by targeting the FOXM1-ADAM17 axis in hepatocellular carcinoma","authors":"","doi":"10.1016/j.cellsig.2024.111467","DOIUrl":"10.1016/j.cellsig.2024.111467","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Efforts have been focused on developing new anti-HCC agents and understanding their pharmacology. However, few agents have been able to effectively combat tumor growth and invasiveness due to the rapid progression of HCC. In this study, we discovered that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid derived from Stephania tetrandra S. Moore, effectively inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells. FAN treatment also led to the suppression of IL6 and IL1β release, as well as the expression of inflammation-related proteins such as COX-2 and iNOS, and the activation of the NF-κB pathway, thereby reducing inflammation-related EMT. Additionally, FAN directly bound to forkhead box protein M1 (FOXM1), resulting in decreased levels of FOXM1 proteins and disruption of the FOXM1-ADAM17 axis. Our <em>in vivo</em> findings confirmed that FAN effectively hindered the growth and lung metastasis of HCCLM3-xenograft tumors. Importantly, the upregulation of FOXM1 in HCC tissue suggested that targeting FOXM1 inhibition with FAN or its inhibitors could be a promising therapeutic approach for HCC. Overall, this study elucidated the anti-tumor effects and potential pharmacological mechanisms of FAN, and proposed that targeting FOXM1 inhibition may be an effective therapeutic strategy for HCC with potential clinical applications.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CAF-secreted LOX promotes PD-L1 expression via histone Lactylation and regulates tumor EMT through TGFβ/IGF1 signaling in gastric Cancer CAF 分泌的 LOX 通过组蛋白乳酸化促进 PD-L1 的表达，并通过 TGFβ/IGF1 信号调节胃癌中肿瘤的 EMT

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-10 DOI: 10.1016/j.cellsig.2024.111462

{"title":"CAF-secreted LOX promotes PD-L1 expression via histone Lactylation and regulates tumor EMT through TGFβ/IGF1 signaling in gastric Cancer","authors":"","doi":"10.1016/j.cellsig.2024.111462","DOIUrl":"10.1016/j.cellsig.2024.111462","url":null,"abstract":"<div><div>In gastric cancer treatment, cancer-associated fibroblasts (CAF) may significantly influence the efficacy of immune checkpoint inhibitors by modulating PD-L1 expression. However, the precise mechanisms remain unclear. This study aims to explore the relationship between CAF and PD-L1 expression, providing new insights for improving PD-L1-targeted therapies.</div><div>Using primary fibroblasts, transcriptome sequencing, ChIP-qPCR, and a lung metastasis model, we discovered that CAF secrete lysyl oxidase (LOX), which activates the TGFβ signaling pathway in gastric cancer cells, thereby promoting insulin-like growth factor 1(IGF1) expression. Upregulation of IGF1 enhances gastric cancer cell migration, epithelial-mesenchymal transition (EMT), and glycolysis. Additionally, we found that lactate accumulation leads to lysine 18 lactylation on histone H3 (H3K18la), which enriches at the PD-L1 promoter region, thus promoting PD-L1 transcription. These findings suggest that CAF may diminish the effectiveness of PD-1/PD-L1 blockade immunotherapy through LOX-induced glycolysis and lactate accumulation. Consequently, we have constructed a model of the interactions among CAF, lactate, and PD-L1 in gastric cancer progression, providing new experimental evidence for PD-L1-based immunotherapy.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of the local renin–angiotensin system in perivascular adipose tissue on vascular health and disease 血管周围脂肪组织中的局部肾素-血管紧张素系统对血管健康和疾病的影响。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-09 DOI: 10.1016/j.cellsig.2024.111461

{"title":"Impact of the local renin–angiotensin system in perivascular adipose tissue on vascular health and disease","authors":"","doi":"10.1016/j.cellsig.2024.111461","DOIUrl":"10.1016/j.cellsig.2024.111461","url":null,"abstract":"<div><div>Perivascular adipose tissue (PVAT) is found locally around blood vessels. It has the ability to release vasoactive chemicals, such as factors that relax and contract blood vessels. PVAT is now recognized as an endocrine organ with metabolic activity and as a “protagonist” for maintaining vascular homeostasis. Angiotensin II, a powerful vasoconstrictor of the renin–angiotensin system (RAS) that can increase blood pressure and vascular tone, is produced locally by PVAT. To mitigate the multiple vascular effects of angiotensin II, PVAT also generates molecules such as angiotensin (1–7), adiponectin, and nitric oxide. Reactive oxygen species and proinflammatory cytokines are produced in greater amounts when PVAT-mediated angiotensin II is present, resulting in endothelial dysfunction, inflammation, atherosclerosis, and other vascular disorders. The anticontractile and procontractile nature of PVAT is frequently disrupted in obese individuals, which increases the production of angiotensin II and decreases the production of anti-inflammatory and vasodilatory factors. These changes in turn exacerbate vascular inflammation, hypertension, and atherosclerosis. PVAT, which is crucial for maintaining vascular homeostasis, loses its anticontractile effect in obesity due to adipocyte hypertrophy, inflammation, and oxidative stress, exacerbating endothelial dysfunction. Overactive RAS in PVAT facilitates the migration and proliferation of vascular smooth muscle cells and atherosclerotic plaques, both of which accelerate the development of atherosclerosis. Targeting PVAT and the local RAS can offer therapeutic benefits in treating hypertension, atherosclerosis, and other vascular diseases. This review highlights the scientific underpinnings of the function of PVAT in regulating the autocrine and paracrine activities of vascular RAS constituents.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Induction, amplification, and propagation of diabetic retinopathy-associated inflammatory cytokines between human retinal microvascular endothelial and Müller cells and in the mouse retina 糖尿病视网膜病变相关炎症细胞因子在人类视网膜微血管内皮细胞和 Müller 细胞之间以及在小鼠视网膜中的诱导、放大和传播。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-09 DOI: 10.1016/j.cellsig.2024.111454

{"title":"Induction, amplification, and propagation of diabetic retinopathy-associated inflammatory cytokines between human retinal microvascular endothelial and Müller cells and in the mouse retina","authors":"","doi":"10.1016/j.cellsig.2024.111454","DOIUrl":"10.1016/j.cellsig.2024.111454","url":null,"abstract":"<div><div>Ocular levels of IL-1β, TNFα, IL-8, and IL-6 correlate with progression of diabetic retinopathy (<strong>DR</strong>). Müller cells (<strong>MC)</strong>, which are crucial to maintaining retinal homeostasis, are targets and sources of these cytokines. We explored the relative capacities of these four DR-associated cytokines to amplify inflammatory signal expression both in and between human MC (<strong>hMC</strong>) and retinal microvascular endothelial cells (<strong>hRMEC</strong>) and in the mouse retina. Of the four cytokines, IL-1β was the most potent stimulus of transcriptomic alterations in hMC and hRMEC in vitro, as well as in the mouse retina after intravitreal injection in vivo. Stimulation with IL-1β significantly induced expression of <em>all four</em> transcripts in hMC <em>and</em> hRMEC. TNFα significantly induced expression of some, but not all, of the four transcripts in each cell, while neither IL-8 nor IL-6 showed significant induction in either cell. Similarly, conditioned media (<strong>CM</strong>) derived from hMC or hRMEC treated with IL-1β, but not TNFα, upregulated inflammatory cytokine transcripts in the reciprocal cell type. hRMEC responses to hMC-derived CM were dependent on IL-1R activation. In addition, we observed a correlation between cytokine expression changes following direct and CM stimulation and NFκB-p65 nuclear translocation in both hMC and hRMEC. Finally, in mice, intravitreal injections of IL-1β, but not TNFα, induced retinal expression of <em>Il1b</em> and <em>CXCL8</em> homologues <em>Cxcl1</em>, <em>Cxcl2</em>, <em>Cxcl3</em>, and <em>Cxcl5,</em> encoding pro-angiogenic chemokines. Our results suggest that expression of IL-1β, TNFα, IL-8, and IL-6 may be initiated, propagated, and sustained by autocrine and paracrine signals in hRMEC and hMC through a process involving IL-1β and NFκB. Targeting these signals may help thwart inflammatory amplification, preventing progression to vision-threatening stages and preserving sight.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulatory role of Heparan sulfate in leptin signaling 硫酸肝素在瘦素信号传导中的调节作用。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-09 DOI: 10.1016/j.cellsig.2024.111456

{"title":"Regulatory role of Heparan sulfate in leptin signaling","authors":"","doi":"10.1016/j.cellsig.2024.111456","DOIUrl":"10.1016/j.cellsig.2024.111456","url":null,"abstract":"<div><div>Leptin, a hormone mainly secreted by adipocytes, has attracted significant attention since its discovery in 1994. Initially known for its role in appetite suppression and energy regulation, leptin is now recognized for its influence on various physiological processes, including immune response, bone formation, and reproduction. It exerts its effects by binding to receptors and initiating an intracellular signaling cascade. Heparan sulfate (HS) is known to regulate the intracellular signaling of various ligands. HS is present as the glycan portion of HSPGs on cell surfaces and in intercellular spaces, with diverse structures due to extensive sulfation and epimerization. Although HS chains on HSPGs are involved in many physiological processes, the detailed effects of HS chains on leptin signaling are not well understood.</div><div>This study examined the role of HS chains on HSPGs in leptin signaling using Neuro2A cells expressing the full-length leptin receptor (LepR). We showed that cell surface HS was essential for efficient leptin signaling. Enzymatic degradation of HS significantly reduced leptin-induced phosphorylation of downstream molecules, such as signal transducer and activator of transcription 3 and p44/p42 Mitogen-activated protein kinase. In addition, HS regulated LepR expression and internalization, as treatment with HS-degrading enzymes decreased cell surface LepR. HS was also found to exhibit a weak interaction with LepR. Enzymatic removal of HS enhanced the interaction between LepR and low-density lipoprotein receptor-related protein 1, suggesting that HS negatively regulates this interaction. In conclusion, HS plays a significant role in modulating LepR availability on the cell surface, thereby influencing leptin signaling. These findings provide new insights into the complex regulation of leptin signaling and highlight potential therapeutic targets for metabolic disorders and obesity.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rheb1 deficiency elicits mitochondrial dysfunction and accelerates podocyte senescence through promoting Atp5f1c acetylation Rheb1 缺乏会导致线粒体功能障碍，并通过促进 Atp5f1c 乙酰化加速荚膜衰老。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-09 DOI: 10.1016/j.cellsig.2024.111451

{"title":"Rheb1 deficiency elicits mitochondrial dysfunction and accelerates podocyte senescence through promoting Atp5f1c acetylation","authors":"","doi":"10.1016/j.cellsig.2024.111451","DOIUrl":"10.1016/j.cellsig.2024.111451","url":null,"abstract":"<div><div>Podocyte senescence can cause persistent podocyte injury and albuminuria in diabetic kidney disease (DKD), but the mechanism remains obscure. In this study, podocyte senescence was confirmed by immunohistochemical staining in podocytes from patients and mice with DKD. Rheb1 knockout in podocytes aggravated podocyte senescence and injury in diabetic mice, but mitigated podocyte injury in mice with podocyte-specific mTORC1 activation induced by Tsc1 deletion. In cultured podocytes, Rheb1 knockdown remarkably accelerated podocyte senescence, independent of mTORC1. Mechanistically, PDH phosphorylation in podocyte was correlated with podocyte senescence in DKD patients. Rheb1 deficiency decreased ATP, mitochondrial membrane potential and partial components of respiratory chain complex, and enhanced ROS production and PDH phosphorylation, which indicates mitochondrial dysfunction, both in vitro and in vivo. Furthermore, Rheb1 interacted with Atp5f1c, and regulated its acetylation under a high-glucose condition. Together, Rheb1 deficiency elicits mitochondrial dysfunction and accelerates podocyte senescence through promoting Atp5f1c acetylation, in an mTORC1-independent manner, which provides experimental basis for the treatment of DKD.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Game-changing breakthroughs to redefine the landscape of the renin-angiotensin-aldosterone system in health and disease. 改变游戏规则的突破，重新定义肾素-血管紧张素-醛固酮系统在健康和疾病中的作用。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-09 DOI: 10.1016/j.cellsig.2024.111459

Pitchai Balakumar, Gowraganahalli Jagadeesh

引用次数: 0

Inhibition of TREM-1 ameliorates angiotensin II-induced atrial fibrillation by attenuating macrophage infiltration and inflammation through the PI3K/AKT/FoxO3a signaling pathway 抑制 TREM-1 可通过 PI3K/AKT/FoxO3a 信号通路减轻巨噬细胞浸润和炎症，从而改善血管紧张素 II 诱导的心房颤动。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-09 DOI: 10.1016/j.cellsig.2024.111458

{"title":"Inhibition of TREM-1 ameliorates angiotensin II-induced atrial fibrillation by attenuating macrophage infiltration and inflammation through the PI3K/AKT/FoxO3a signaling pathway","authors":"","doi":"10.1016/j.cellsig.2024.111458","DOIUrl":"10.1016/j.cellsig.2024.111458","url":null,"abstract":"<div><div>Inflammation and infiltration of immune cells are intricately linked to the pathogenesis of atrial fibrillation (AF). Triggering receptor expressed on myeloid cells-1 (TREM-1), an enhancer of inflammation, is implicated in various cardiovascular disorders. However, the precise role and potential mechanisms of TREM-1 in the development of AF remain ambiguous. Atrial samples from patients with AF were used to assess the expression levels of TREM-1. An angiotensin II (Ang II)-induced AF mouse model was established to assess the functionality of TREM-1. Cardiac function and AF inducibility were assessed through echocardiography, programmed transvenous cardiac pacing, and atrial electrophysiological mapping. Peripheral blood and atrial inflammatory cells were assessed using flow cytometry. Using histology, bulk RNA sequencing, biochemical analyses, and cell cultures, the mechanistic role of TREM-1 in AF was elucidated. TREM-1 expression was upregulated and co-localized with macrophages in the atria of patients with AF. Pharmacological inhibition of TREM-1 decreased Ang II-induced atrial enlargement and electrical remodeling. TREM-1 inhibition also ameliorated Ang II-induced NLRP3 inflammasome activation, inflammatory factor release, atrial fibrosis, and macrophage infiltration. Transcriptomic analysis revealed that TREM-1 modulates Ang II-induced inflammation through the PI3K/AKT/FoxO3a signaling pathway. In vitro studies further supported these findings, demonstrating that TREM-1 activation exacerbates Ang II-induced inflammation, while overexpression of FoxO3a counteracts this effect. This study discovered the critical role of TREM-1 in the pathogenesis of AF and its underlying molecular mechanisms. Inhibition of TREM-1 provides a new therapeutic strategy for the treatment of AF.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GDF15 enhances anoikis resistance and metastasis of gastric cancer through protective autophagy GDF15通过保护性自噬增强胃癌的抗厌氧菌性和转移性

IF 4.4 2区生物学

Cellular signalling Pub Date : 2024-10-09 DOI: 10.1016/j.cellsig.2024.111457

引用次数: 0