Journal of Cell Communication and Signaling最新文献

CEP162, a 162-kDa centrosome protein, is a crucial centrosomal adapter, mediating cell differentiation and polarization. CEP162 maintains mitosis by dynamically stabilizing microtubules. CEP162 promotes the transition zone (TZ) assembly in the basal body through interaction with CEP131, CEP290, and axoneme microtubules as well as the distal centriole. TZ ensures the normal distribution of soluble proteins between the cytoplasm and cilia. It also facilitates retinal development and sperm flagellar motility. However, fluctuations in TZ permeability caused by abnormal expression of CEP162, including truncated mutations and naturally occurring mutations, lead to cilia abnormality and dysfunction in ciliogenesis through the regulation of intraflagellar transport, resulting in retinal degeneration and infertility. LncRNAs can induce SNP events in the CEP162 transcript by altering alternative splicing. Naturally occurring mutations are closely linked to retinal ciliopathy and diabetic retinopathy. This review summarizes the latest research progress to better understand the biology and pathophysiology of CEP162 and the clinical manifestations caused by CEP162 variants.

Small extracellular vesicles (sEVs) are considered promising gene-delivery vehicles for the treatment of osteoarthritis (OA). This study aimed to explore the molecular mechanism by which M2 macrophage-derived sEVs (M2-sEVs) modulate chondrocyte proliferation and apoptosis, thereby affecting OA progression. M2 macrophages were successfully induced, and M2-sEVs were successfully isolated. The sEVs were small vesicles with diameters ranging from 50 to 150 nm. The exosomal markers, including CD9, CD63, and CD81, were highly expressed, whereas the negative marker calnexin was absent in M2-sEVs. M2-sEVs effectively alleviated OA tissue and chondrocyte damage in both in vivo and in vitro models, evidenced by reduced rat knee joint injury, increased chondrocyte viability, and decreased chondrocyte apoptosis and extracellular matrix (ECM) degradation. Furthermore, M2-sEVs decreased the levels of pro-inflammatory cytokines IL-6 and TNF-α. Osteopontin (OPN) was upregulated within rats with OA and IL-1β-induced chondrocytes. Silencing of OPN exacerbated IL-1β-induced chondrocyte damage and partially abrogated the therapeutic effects of M2-sEVs. Additionally, M2-sEVs enhanced OPN expression and activated CD44 and the PI3K/AKT signaling pathway. In conclusion, M2-sEVs promoted OPN expression to improve knee joint tissue damage in rats with OA and chondrocyte damage. This protective effect of M2-sEVs might be associated with the activation of CD44 and the PI3K/AKT signaling.

Chemoresistance and immune evasion remain significant barriers to effective esophageal cancer (EC) treatment. This study explores the mechanistic role of extracellular vesicles (EVs) delivering LncRNA HOTAIR in modulating these processes. Using transcriptomic profiling, LncRNA HOTAIR was identified as a critical factor in EC progression. Its interaction with miR-375 was examined via luciferase reporter assays and RNA immunoprecipitation. Paclitaxel-resistant EC cells were treated with EVs containing HOTAIR, and the functional impact on proliferation, migration, invasion, and immune response was assessed through in vitro and in vivo models. LncRNA HOTAIR in EVs enhanced paclitaxel resistance by suppressing miR-375 and increasing CDH2 expression. Furthermore, HOTAIR promoted immune escape by upregulating PD-L1, impairing T-cell-mediated cytotoxicity. These changes were validated in patient-derived EC models. This study demonstrates that EV-LncRNA HOTAIR mediates chemoresistance and immune evasion in EC by targeting the miR-375/CDH2 axis. These findings provide a foundation for novel therapeutic interventions targeting EV-HOTAIR.

Hepatocellular carcinoma (HCC), a severe consequence of hepatitis C virus infection, is significantly influenced by the virus’s non-structural protein 3 (NS3). This study employed transcriptome sequencing to explore the role of NS3 in promoting HCC progression by comparing gene expression profiles between HCV-infected HCC tissues and healthy liver controls. Key genes regulated by NS3 were identified and validated with quantitative reverse transcription PCR (RT-qPCR) and western blot analyses. Functionality assays, including CCK-8, BrdU, and Transwell migration and invasion tests, were performed to evaluate the effects of NS3 on HCC cell proliferation, migration, and invasion. Further investigation through a dual-luciferase reporter and RNA pull-down assays revealed that NS3 specifically upregulates circ_0001175. This circular RNA interacts with and inhibits miR-130a-5p, diminishing its regulatory impact on P53 by modulating the MDM4 pathway, thereby promoting oncogenic characteristics. The findings highlight the NS3-induced circ_0001175/miR-130a-5p/MDM4/P53 pathway as a potential therapeutic target, offering promising directions for treatment strategies in HCV-related HCC.

This study explored the possible effect of transcription factor GTF2I on the differentiation of osteoclasts and its regulation on the miR-134-5p/MAT2A axis. RANKL-induced osteoclasts were measured for expressions of GTF2I, miR-134-5p, and MAT2A. The number and size of osteoclasts were assessed after TRAP staining. The expressions of osteoclast differentiation biomarkers, NFATC1, TRAP, and CTSK, were detected as well. The relationships of the GTF2I/miR-134-5p/MAT2A axis were verified by ChIP, dual luciferase, and RNA pull-down assay. In vivo experiments were conducted on ovariectomized (OVX)-treated mice to determine the effect of GTF2I overexpression on osteoclast differentiation and bone loss. RANKL-induced osteoclasts had suppressed expressions of GTF2I and miR-134-5p and increased expression of MAT2A. GTF2I overexpression or miR-134-5p overexpression contributed to decreased cell number and size and suppressed cell differentiation, whereas such an effect can be abolished by overexpression of MAT2A. GTF2I can bind the miR-134-5p promoter to regulate its expression, whereas miR-134-5p can negatively regulate MAT2A expression. The protective effect of GTF2I overexpression against bone loss and cell differentiation was verified by in vivo experiments. Collectively, these results indicate that GTF2I can mediate miR-134-5p expression to increase MAT2A expression, contributing to the suppression of osteoclast differentiation.

Alzheimer's disease (AD) is the most common form of dementia and is characterized by progressive memory loss and cognitive decline, affecting behavior, speech, and motor abilities. The neuropathology of AD includes the formation of extracellular amyloid-β plaques and intracellular neurofibrillary tangles of phosphorylated tau, along with neuronal loss. Although neuronal loss is an AD hallmark, cell–cell communication between neuronal and non-neuronal cell populations maintains neuronal health and brain homeostasis. To study changes in cell–cell communication during disease progression, we performed snRNA-sequencing of the hippocampus from female 3xTg-AD and wild-type littermates at 6 and 12 months. We inferred differential cell–cell communication between 3xTg-AD and wild-type mice across time points and between senders (astrocytes, microglia, oligodendrocytes, and OPCs) and receivers (excitatory and inhibitory neurons) of interest. We also assessed the downstream effects of altered glia–neuron communication using pseudobulk differential gene expression, functional enrichment, and gene regulatory analyses. We found that glia–neuron communication is increasingly dysregulated in 12-month 3xTg-AD mice. We also identified 23 AD-associated ligand–receptor pairs that are upregulated in the 12-month-old 3xTg-AD hippocampus. Our results suggest increased AD association of interactions originating from microglia. Signaling mediators were not significantly differentially expressed but showed altered gene regulation and transcription factor activity. Our findings indicate that altered glia–neuron communication is increasingly dysregulated and affects the gene regulatory mechanisms in neurons of 12-month-old 3xTg-AD mice.

Circular RNAs (circRNAs) are RNA molecules frequently involved in tumorigenesis. This research study focuses on the relevance of hsa_circ_515 (circ_515) to non-small cell lung cancer (NSCLC) progression and the downstream targets involved. Differentially expressed circRNAs in NSCLC were screened using a GSE158695 dataset. Circ_515 was overexpressed and indicated poor outcomes in patients with NSCLC. Knockdown of circ_515 repressed proliferation and invasiveness, while potentiated cell cycle arrest and apoptosis of NSCLC cells, and upregulation of circ_515 led to converse trends. The candidate downstream transcripts of circ_515 were explored using integrated bioinformatic analyses. Ectopic expression of miR-296-5p reduced the malignance of NSCLC cells. Circ_515 sequestered miR-296-5p and blocked its suppressive role in RING finger protein 44 (RNF44) expression. Downregulation of RNF44 counteracted the oncogenic effects of circ_515. In vivo, the anti-tumor effects of circ_515 knockdown were reversed by miR-296-5p, while the tumor-promoting effects of circ_515 upregulation were abolished by RNF44 knockdown. All in all, our findings demonstrate that circ_515 sequesters miR-296-5p and elevates RNF44 expression to encourage the NSCLC progression. This study might provide new thoughts on NSCLC management.

Diabetic retinopathy (DR), as the main ophthalmic complication of diabetes mellitus, is a major eye disorder contributing to blindness. Oxidative stress and inflammation in retinal Müller cells participate in the pathogenesis of DR. This work aims to study the biological role of moscatilin in the progression of DR and the underlying mechanism. High glucose (HG)-stimulated mouse primary retinal Müller cells and high-fat diet + streptozotocin (STZ)-induced DR mouse models were constructed as in vitro and in vivo models, respectively. The effects of moscatilin treatment on oxidative stress and inflammation in HG-stimulated Müller cells and DR mice were evaluated by detecting intracellular reactive oxygen species production, malondialdehyde levels, superoxide dismutase and catalase activities, glutathione/oxidized glutathione ratio, as well as proinflammatory cytokine levels through CM-H₂DCFDA staining, commercial kits, and enzyme-linked immunosorbent assay. Dual immunofluorescence staining of glial fibrillary acidic protein and vimentin was used to evaluate the development of Müller cells in mouse retinas. The activity of p38 mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK) and nuclear factor kappa-B (NF-κB) signaling pathway was assessed through western blotting and immunofluorescence staining. Moscatilin pretreatment prevented HG-induced decrease in Müller cell viability. Moscatilin mitigated oxidative stress, inflammation, and extracellular matrix remodeling in HG-stimulated Müller cells and DR mice. Mechanically, moscatilin reduced the levels of receptor for advanced glycation end products, phosphorylated I-kappa-B-alpha, p-p65 NF-κB, p-p38 MAPK, and p-JNK in both HG-stimulated Müller cells and DR mice. Moscatilin plays an antioxidant and anti-inflammatory role in DR by inhibiting the p38 MAPK/JNK and NF-κB signaling pathways.

I am deeply honored to have been appointed as the new Editor-in-Chief (EiC) of the Journal of Cell Communication and Signaling (JCCS). As I step into this role of EiC, I look forward to continuing collaborating with the dedicated readership, expert reviewers, editorial board members, and the publisher of the journal to advancing knowledge in research on cell communication and signaling governing key biochemical and physiological processes both in normal and pathological conditions. JCCS remains dedicated to publishing cutting-edge research, while continuously expanding the range of submissions and refining the review and editorial processes to ensure a more inclusive and impactful scientific contribution. I would like to thank the founder of JCCS and my predecessor EiC, Prof. Bernard Perbal and his right hand Annick Perbal for their enormous contribution to JCCS, and their crucial role shaping the Journal into a platform that welcomes innovative research and enhances our understanding of cellular communication networks in health and diseases and for steering us safely over the last two decades through the increasingly challenging scientific publication landscape. In this editorial, I share some of my reflections, ideas, acknowledgments, and aspirations for the future of the journal.

Functional expression of the calcium-sensing receptor (CaSR) in calcitropic tissues, for example, parathyroid glands and kidneys, is important for maintaining Ca²⁺ homeostasis. It is also established that the CaSR is present in tissues previously thought to be noncalcitropic and this review discusses the role of the CaSR in vascular function, focusing mainly on contractility but also outlining its role in cell proliferation and calcification. Stimulation of the CaSR by extracellular Ca²⁺ concentration ([Ca²⁺]_o) on perivascular sensory nerves and vascular endothelial cells is associated with vasodilatation through the release of vasoactive substances and stimulation of IK_Ca channels and nitric oxide synthesis, respectively, which mediate endothelium-derived hyperpolarizations and activation of BK_Ca channels and K_ATP channels in vascular smooth muscle cells (VSMCs). CaSR-induced vasoconstrictions are mediated by the CaSR expressed in VSMCs, which are coupled to the G_q/11 protein-coupled pathway. In addition, the CaSR expressed on VSMCs also regulates proliferation and calcification. Consequently, the CaSR has been implicated in regulating systemic and pulmonary blood pressure and calcimimetics and calcilytics are potential therapeutic targets for cardiovascular diseases, such as hypertension, pulmonary artery hypertension, and atherosclerosis.