Cell Biology International最新文献

Prior studies have identified atypical expression of protein tyrosine phosphatase receptor type E (PTPRE) in animal models of salt-sensitive hypertension (SSH). This study investigates PTPRE's role in SSH and clarifies its mechanism of action. Through gene knockdown and overexpression of PTPRE in DOCA-salt hypertensive mice, we assessed the vasomotor function of aortic rings. PTPRE-induced phenotypic changes in vascular smooth muscle cells (VSMCs) were identified using phenotypic markers and related functional parameters. The phosphorylation levels of the MAPK signaling pathway subfamilies were assessed using Western blot analysis. Upregulation of PTPRE was observed in the VSMCs of DOCA-salt-induced SSH mice. This upregulation was associated with impaired vasoconstriction and vasodilation of arteries, as well as increased blood pressure (BP) (all p < 0.01). Altering PTPRE expression via knockdown and overexpression markedly affected the expression of synthetic (OPN) and contractile (α-SMA and SM22α) phenotype markers in the aortic media and VSMCs of SSH mice (all p < 0.01). Moreover, PTPRE expression influenced the phosphorylation activation within the MAPK signaling pathway. Specifically, regulation of PTPRE expression in SSH modulated the phosphorylation of the JNK and p38 MAPK subfamilies, along with the upstream phosphorylation of MKK3 and MKK6 (all p < 0.05). Our findings indicate that PTPRE significantly contributes to vascular vasomotor dysfunction and the phenotypic transformation of VSMCs in SSH. This involvement in SSH development seems to occur mainly via modulation of the JNK and p38 MAPK pathways.

Inflammation is associated with disease progression and frequent exacerbations of chronic obstructive pulmonary disease (COPD). The cell crosstalk plays a central role in initiating and maintaining inflammation. This study aimed to establish a cell coculture model simulating the inflammatory microenvironment, and investigate the mechanism of cell communication in COPD. The cell type, and cell crosstalk in normal and COPD were analyzed based on single-cell RNA sequencing data from GEO database. Then, lipopolysaccharide (LPS)-induced coculture model of alveolar epithelial cells (A549), human umbilical vein endothelial cells (HUVECs), and macrophages (THP-1) was established using Transwell. Cell viability and cytokine profiles were measured after LPS exposure. Subsequently, monoculture and coculture systems were designed to compare cytokines release. Furthermore, the gene expressions of cytokines and ultrastructure of cells were observed, and phenotype of THP-1 cells was detected. Finally, the protein expression of NF-κB, MAPK, GSK3β and mTOR signaling pathways were analyzed. The results indicated that cell crosstalk signaling between epithelial cells, endothelial cells, and macrophages is much stronger in COPD. Cytokines secretion increased significantly after LPS treatment for 24 h. IFN-γ, IL-2, and IL-6; TNF-α, IFN-γ, and IL-2; and TNF-α, IL-1β, IL-6, IFN-γ, IL-8 and IL-12 were secreted mainly by A549, HUVECs, and THP-1 cells, respectively. The NF-κB and GSK3β signaling pathways were activated in cocultured cells. These findings indicated that cytokines from HUVECs and A549 cells promoted the M1 phenotypic differentiation of THP-1 cells. LPS amplifies the inflammation of co-culture cells by promoting cytokines release via activating the NF-κB and GSK3β signaling pathways.

Brain ischemia induces neuronal apoptosis, a key event in stroke pathology, but the underlying mechanisms remain incompletely understood. This study investigates the role of the volume-regulated anion channel subunit leucine-rich repeat-containing protein 8 A (LRRC8A) in ischemia-induced neuronal damage. In a rat model of middle cerebral artery occlusion (MCAO) and in cultured neurons under oxygen-glucose deprivation (OGD), ischemia/hypoxia rapidly upregulated LRRC8A expression in apoptotic neurons. Knockdown of lrrc8a via small interfering RNA (siRNA) attenuated brain infarction, improved neurological deficits, and reduced neuronal apoptosis. Mechanistically, lrrc8a knockdown suppressed the activation of the mitochondrial Bax/Bcl-2/Caspase-9/Caspase-3 apoptotic pathway. Furthermore, lrrc8a knockdown reversed OGD-induced hyperactivation of NMDA receptors (NMDARs) and weakened the enhanced interaction between LRRC8A and the obligatory NMDAR subunit GluN1, which was predicted by structural modeling. These findings reveal that cerebral ischemia upregulates neuronal LRRC8A, which may promote NMDAR hyperactivity via interaction with GluN1, thereby triggering mitochondrial apoptosis. LRRC8A represents a potential therapeutic target for mitigating neuronal apoptosis in ischemic stroke.

As a member of the inflammasome, NLRP1 has been reported to play roles in some cancers. However, the effect of NLRP1 in hepatocellular carcinoma (HCC) remains elusive. This study aims to explore the effect and mechanism of NLRP1 on HCC. The effect of NLRP1 on HCC cell malignant behaviors was investigated by using CCK-8, EdU, colony formation, flow cytometry, wound healing and transwell invasion assays. The expression levels of relevant proteins were measured by western blot and immunohistochemical assay. In addition, tumor formation was detected using in vivo xenograft model in BALB/c nude mice. We discovered that NLRP1 was lowly expressed in HCC, and the increased NLRP1 expression was correlated with good prognosis in HCC patients. NLRP1 inhibited HCC cell proliferation, migration, invasion, epithelial-mesenchymal transition, and disrupted fatty acid metabolism. Moreover, NLRP1 knockdown reversed GATA3-mediated suppression of proliferation and migration in HCC cells. Besides, NLRP1 or GATA3 was demonstrated to inhibit HCC cell proliferation and migration via inhibiting Hedgehog signaling, which verified by the rescue experiments. Additionally, NLRP1 also inhibited tumor growth in nude mice. Our study demonstrated that GATA3-NLRP1 axis could inhibit proliferation, migration, and invasion of HCC cells, and disrupt fatty acid metabolism through suppressing Hedgehog signaling, highlighting the anti-cancer role of NLRP1 in HCC.

We previously showed that inhibition of the NF-κB signaling pathway in mesenchymal stromal cells (MSCs) (NKI-MSCs) induces quiescence in co-cultured hematopoietic stem cells (HSCs). This led us to investigate whether NKI-MSCs exert similar growth-inhibitory effects on leukemic cells. We found that both NKI-MSCs and their secretome induce cell cycle arrest in KG1a cells, a cell line of acute myeloid leukemia (AML) origin. Surprisingly, the extracellular vesicles (EVs) isolated from NKI-MSCs supported the proliferation of KG1a cells. This is perhaps the first report showing the opposite effects of MSCs and the EVs secreted by them. Further analysis revealed that microvesicles (MVs) from NKI-MSCs inhibited KG1a cell growth and induced apoptosis, whereas exosomes (Exos) supported proliferation. Our findings could have clinical implications. NKI-MVs, having apoptosis-inducing activity, could serve as an adjunct, off-the-shelf biologic to limit AML growth, enabling reduced-intensity chemotherapy in elderly patients and patients having co-morbidities. NF-κB inhibitors have been tried as chemotherapeutic agents for treating AML patients. However, systemic inhibition of NF-κB may also affect the bone marrow resident MSCs, which in turn could produce EVs supporting the proliferation of AML blasts. Our data could explain the inadequate clinical effectiveness of NF-κB inhibitors in treating AML, and also raise a concern for the systemic use of NF-κB inhibitors in the therapeutic regimen.

Male infertility is a multifactorial condition affecting approximately 8%–12% of reproductive-age couples worldwide, with male factors contributing to nearly half of all cases. Traditional treatments often offer limited efficacy, especially in cases involving testicular toxicity, diabetes-related erectile dysfunction, and aging-associated reproductive decline. In recent years, mesenchymal stem cell-derived exosomes (MSC-EXOS) have emerged as a promising cell-free therapeutic approach due to their ability to carry bioactive molecules—such as proteins, lipids, and microRNAs—that modulate inflammation, oxidative stress, apoptosis, and tissue regeneration. This review highlights the pathophysiology of key male reproductive disorders and explores the therapeutic potential of MSC-EXOS in preclinical models. Evidence demonstrates that exosomes from adipose tissue, bone marrow, and umbilical cord MSCs can improve spermatogenesis, restore hormonal balance, enhance vascular function, and repair damaged testicular architecture. While findings are encouraging, challenges remain regarding optimal delivery, dosage, and translation to clinical settings. This review provides the most comprehensive synthesis of preclinical evidence to date demonstrating that mesenchymal stem cell-derived exosomes consistently outperform traditional MSC therapy across multiple male reproductive disorders while offering superior safety and scalability. These findings establish exosomes as a transformative cell-free platform ready for clinical translation in male infertility, warranting further investigation through clinical trials and mechanistic studies.

Selective migration of tumors to particular organs, referred to as organ tropism, is not arbitrary but guided by intricate molecular interactions and a complex network of various secretory molecules. This site-specific migration is modulated by molecular crosstalk, where cytokines and other effectors help tumor cells adapt to and colonize a new organ by reshaping their epigenetics. It is well established that breast and colorectal cancers, for instance, can epigenetically modify themselves to show a preference for the brain, bones, lungs, and liver but the key modulators are still elusive. Here, we have discussed the key mechanisms, including the critical interacting molecules, cytokines, and pathways that drive this site-specific tropism-based colonization. By synthesizing current knowledge, we highlight central players in this process and discuss their potential as therapeutic targets to inhibit metastasis and improve patient outcomes.

Myxomycetes are remarkable organisms, capable of strikingly complex behaviors and exceptional wound healing, yet the molecular mechanisms underlying their immunity and regenerative capacities remain largely unexplored. In this study, we provide the first evidence that these unique organisms could possess a protein resembling macrophage migration inhibitory factor (MIF). Using a custom MIF polyclonal antibody, we detected signals specifically along the pseudopodia of two myxomycetes species, Physarum polycephalum and Badhamia utricularis. Western blot analysis revealed three distinct bands consistent with potential monomeric, dimeric, and trimeric forms of the protein. Notably, following mechanical injury, this protein accumulated at the sites of damage, suggesting a potential role in injury sensing and tissue repair. In contrast, exposure to GFP-expressing Erwinia carotovora did not alter its localization, indicating that this response is likely independent of non-self-recognition. Although current genomic resources for these myxomycetes do not contain annotated MIF sequences, our findings highlight a previously unrecognized, injury-responsive protein in these organisms. This discovery underscores the sophisticated regenerative capacities of myxomycetes and opens new avenues for exploring immune and repair mechanisms in this ancient and fascinating species.