Journal of Cell Communication and Signaling最新文献

Osteoarthritis (OA) is a prevalent degenerative joint disease driven by inflammation and cartilage degradation. The NOD-like receptor protein 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) pathway are central to OA-associated inflammation. Sirtuin 2 (SIRT2), an NAD⁺-dependent deacetylase, regulates inflammation and oxidative stress but its role in OA is not fully understood. This study aims to elucidate how SIRT2 modulates the NLRP3/NF-κB signaling axis to promote cartilage repair in OA. In vivo and in vitro experiments were conducted using OA mouse models and chondrocyte cultures. Single-cell RNA sequencing was performed to identify differentially expressed genes, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. SIRT2's impact on NLRP3 and NF-κB was assessed using Western blotting (WB), real-time PCR, co-immunoprecipitation (Co-IP), and chromatin immunoprecipitation (ChIP-qPCR). SIRT2 was found to deacetylate NF-κB p65, inhibiting NLRP3 activation and reducing inflammatory cytokines. SIRT2 overexpression enhanced chondrocyte proliferation, DNA repair, and mitochondrial function while decreasing reactive oxygen species production. In vivo, SIRT2 significantly improved cartilage repair in OA mice with NLRP3 overexpression attenuating its protective effects. SIRT2 promotes cartilage repair in OA by regulating the NF-κB/NLRP3 axis, reducing inflammation and oxidative stress. This highlights SIRT2 as a potential therapeutic target for OA.

Knee osteoarthritis (KOA) is a progressive disease featured by cartilage damage. This study attempts to explore the role of nuclear binding SET domain 1 (NSD1) in KOA cartilage ferroptosis, thereby finding a new target for KOA treatment. Pathological changes, cartilage damage, and inflammatory cytokine levels in the established KOA mouse model were assessed. Primary mouse knee chondrocytes were separated, cultured, and challenged with IL-1β to establish in vitro KOA models. Cell viability was determined, Reactive oxygen species levels and ferroptosis-related factors were measured after interventions with NSD1, krüppel-like factor 9 (KLF9), and acyl-CoA synthetase long-chain family member 4 (ATG14). Furthermore, the enrichment of NSD1 and H3K36me2 on the KLF9 promoter as well as the enrichment of KLF9 on the ATG14 promoter was analyzed. Binding site between KLF9 and ATG14 promoter was assessed. NSD1 was downregulated in KOA mouse cartilage tissues and IL-1β-challenged chondrocytes. KOA severity was alleviated, chondrocyte viability was promoted, and ferroptosis was quenched after NSD1 overexpression. NSD1 strengthened H3K36me2 to upregulate KLF9 expression, and KLF9 transcriptionally activated ATG14 expression. KLF9 or ATG14 knockdown could both partially reverse the protective role of NSD1 overexpression on KOA cartilage ferroptosis. NSD1 enhanced KLF9 expression to improve ATG14 expression via H3K36me2 modification, thus relieving KOA cartilage ferroptosis.

Diabetic foot ulcer (DFU) is a severe diabetes complication characterized by impaired angiogenesis and chronic inflammation, leading to delayed wound healing. Exosomes (Exo) derived from hypoxic adipose-derived stem cells (H-ADSCs-Exo) show potential as therapeutic carriers. This study investigates the role of H-ADSCs-Exo carrying miR-100-5p in DFU healing. ADSCs were isolated, characterized, and their Exo analyzed via transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Transcriptome sequencing identified miR-100-5p as a key modulator of angiogenesis and inflammation. In vitro, H-ADSCs-Exo enhanced human umbilical vein endothelial cell and fibroblast proliferation, migration, and tube formation. In a rat DFU model, H-ADSCs-Exo administration reduced ulcer size, increased angiogenesis (VEGF/CD31 expression), and decreased inflammatory markers (TNF-α, IL-6). miR-100-5p overexpression further amplified these effects, demonstrating its critical role in Exo-mediated healing. These findings highlight the therapeutic potential of H-ADSCs-Exo in DFU treatment, offering insights into cell signaling mechanisms and paving the way for miRNA-based regenerative therapies.

General anesthetic exposure during pregnancy has neurotoxic effects on the developing brain, causing long-term cognitive dysfunction in the offspring. Sevoflurane exposure during mid-gestation results in premature differentiation of neural stem cells (NSCs), being the crucial factor affecting normal hippocampal functions and contributing to neurocognitive impairment. However, the related molecular mechanism remains unclear. For in vivo assays, pregnant rats were exposed to 3% sevoflurane once on gestational day 14 (G14) or 3 times on G13, 14, and 15 (2 h per day). For in vitro assays, primary rat NSCs were isolated from fetal hippocampus tissues at 24 and 72 h after birth and on postnatal day 28. NSCs were transfected with GRIN2B or KIF17 overexpression plasmids before exposure to 4.1% sevoflurane for one or three consecutive days (2 h per day). Multiple sevoflurane exposures during the mid-trimester triggered NSC premature differentiation and decreased GRIN2B and KIF17 expression in the hippocampus of offspring rats and primary rat NSCs. GRIN2B or KIF17 overexpression attenuated sevoflurane-induced NSC premature differentiation. GRIN2B interacted with KIF17, and KIF17 silencing reversed the inhibition of GRIN2B overexpression on NSC early differentiation. GRIN2B alleviates NSC premature differentiation induced by repeated mid-gestational sevoflurane exposure via interaction with KIF17.

Naa10p disrupts the protective mitochondrial UCP1 pathway in acute pancreatitis (AP). This study demonstrates that Naa10p upregulation in AP correlates with decreased UCP1 expression and increased reactive oxygen species production. Silencing Naa10p improved cell survival, suppressed inflammation, and enhanced UCP1 levels by promoting PGC-1α/Pparγ2 interaction. Co-immunoprecipitation and luciferase assays confirmed that Naa10p inhibits UCP1 promoter activation. This study reveals the significance of Naa10p as a potential target for the treatment of AP and provides a new idea for the intervention of pancreatic inflammatory diseases.

Cell lines are essential tools in biomedical research and drug discovery, often substituting for tissues or organs of origin. However, frequent misidentification and cross-contamination pose major quality control challenges, leading to unreliable data, hindering scientific progress, and impacting clinical translation. Even authenticated cell lines may undergo genetic and phenotypic changes over time, affecting experimental outcomes. To promote transparency, reproducibility, and rigor, the Journal of Cell Communication and Signaling (JCCS) reaffirms its commitment to best practices in cell line authentication and validation, in alignment with Wiley's publishing ethics. Authors submitting manuscripts must provide comprehensive cell line details, including species, sex, tissue origin, name, and Research Resource Identifier. They are also required to document the source, acquisition date, and authentication methods such as short tandem repeat (STR) profiling and adventitious agent testing, including mycoplasma screening. By enforcing strict guidelines, JCCS seeks to improve research integrity, reduce erroneous findings, and enhance reproducibility. This initiative not only strengthens the reliability of published studies but also supports the broader scientific community in accelerating discovery and translating research into clinical advances for better human health.

To elucidate the oncogenic role of angio-associated migratory cell protein (AAMP) in colorectal cancer (CRC) and its mechanistic interplay with phosphoglycerate kinase 1 (PGK1). AAMP expression was analyzed in CRC and normal tissues (tissue microarrays-immunohistochemical/Western blot). Functional impacts were assessed via siRNA knockdown and lentiviral overexpression in CRC cell lines (proliferation: CCK-8/3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide/clonogenic assays; tumorigenesis: xenografts). Molecular mechanisms were explored through co-immunoprecipitation, phosphorylation assays, and Ribonucleic Acid (RNA) sequencing. AAMP was significantly upregulated in CRC versus normal tissues (p < 0.05), correlating with poor patient survival. AAMP knockdown suppressed CRC cell proliferation, colony formation, and xenograft tumor growth, whereas overexpression exacerbated these phenotypes. Mechanistically, AAMP directly bound PGK1 and enhanced its phosphorylation (p-PGK1), driving CRC proliferation. PGK1 silencing abrogated AAMP-mediated proliferative effects. RNA sequencing revealed AAMP modulation of immune-related pathways (Tumor Necrosis Factor, IL-17, Jak-STAT) and key proteins (EGFR, RPL10, NOD2), suggesting dual roles in proliferation. AAMP promotes CRC progression through PGK1 phosphorylation-dependent metabolic activation, proposing the AAMP-PGK1 axis as a therapeutic target for advanced CRC.

Membranous nephropathy (MN) is a common glomerular disease characterized by podocyte injury. Although previous studies highlighted the leucine-rich repeat-containing 55/big potassium (LRRC55/BK) channel axis in Ang II-induced apoptosis, our study further investigates the upstream regulation by nuclear factor of activated T-cells 3 (NFATc3) and its role in extracellular matrix (ECM) remodeling. Using an Ang II-induced podocyte injury model, we found that NFATc3 overexpression promoted LRRC55 transcription, increased BK channel activity, and elevated intracellular calcium, thereby exacerbating podocyte apoptosis and impairing migration. RNA-seq and functional assays revealed significant upregulation of ECM-related genes, with enhanced fibronectin and collagen I deposition. Patch-clamp experiments confirmed BK channel activation was LRRC55-dependent. In vivo, NFATc3 knockdown attenuated renal injury, restored podocyte markers (nephrin, WT1, synaptopodin), and alleviated proteinuria and fibrosis, whereas LRRC55 overexpression or BK agonist NS1619 reversed these effects. These findings reveal that NFATc3 aggravates Ang II-induced podocyte injury through transcriptional regulation of LRRC55 and activation of the BK channel, contributing to ECM remodeling and glomerular dysfunction. Our results offer mechanistic insight into MN progression and suggest the NFATc3/LRRC55/BK axis as a potential therapeutic target.

Diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus, involves complex molecular pathways and the ceRNA regulatory network. Integration of diabetes-related circRNA datasets identified circ_0012856 as pivotal via least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms. Functional enrichment analyses elucidated its involvement in DPN pathogenesis. In vitro studies showed circ_0012856 regulating EZH2 and STAT3 expressions, inhibiting autophagy, and promoting microglial M1 polarization. In vivo, experiments revealed silencing circ_0012856 alleviating DPN symptoms in diabetic mice. Overall, circ_0012856 acts as a miR-124 sponge, affecting key pathways in DPN progression and providing potential therapeutic targets.

The development of B-ALL alters the bone marrow microenvironment influencing disease progression and response to therapy. The aggressiveness of particular B-ALL subtypes could be related to specific mechanisms used to reprogram bone marrow stromal cells. The purpose of this study is to compare the effect of two B-ALL subtypes, with opposite prognosis, on mesenchymal stem cells (MSC) functions and the consequences on leukemic cell properties. We have established an in vitro leukemic niche (LN) by co-culturing MSC with REH (favorable prognosis) or SUP-B15 (poor prognosis) B-ALL cell lines and examined leukemic-induced MSC reprogramming and its impact on leukemic cells properties and drug resistance. The aggressive SUP-B15 cell line showed faster and stronger adherence to MSC and increased migration to CXCL12 and LN secretome, compared to REH cells. SUP-B15 cell proliferation was reduced but modulated over time. No differences in MSC senescence induction or recovery were observed between both cell lines. Interestingly, the SUP-B15 LN secretome was enriched in IL-6, IL-8, CCL2 and MIF. MSC pre-incubated with CCL2 showed increased MSC senescence but this did not alter protection against cytotoxic drugs. On the contrary, MSC self-renewal and adipogenic differentiation were also increased in the aggressive SUP-B15 cell line, strengthening protection against the cytotoxic drugs vincristine, methotrexate and doxorubicin. This study showed that the aggressiveness of certain leukemia subtypes is also associated with specific changes induced in MSC secretome and stemness that have an impact on specific properties of leukemic cells, improving LN fitness and ability to survive to cytotoxic drugs.