Ask about this productRelated genes to: TWEAK
- Gene:
- TNFSF12 NIH gene
- Name:
- TNF superfamily member 12
- Previous symbol:
- -
- Synonyms:
- TWEAK, DR3LG, APO3L
- Chromosome:
- 17p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-04
- Date modifiied:
- 2019-04-23
Related products to: TWEAK
Related articles to: TWEAK
- Intestinal barrier dysfunction and mucus layer abnormalities are central features of inflammatory bowel disease, yet the epithelial mechanisms regulating goblet cell function remain incompletely understood. The TWEAK/Fn14 pathway is involved in intestinal inflammation, but its role in small intestinal epithelial responses, particularly in goblet cells, has not been fully clarified. In this study, we investigated TWEAK/Fn14 signaling using mouse small intestinal epithelial organoids. Fn14 was expressed in MUC2-positive cells in intestinal tissue, with staining preferentially observed toward the mucin-facing region. Fn14 staining was also observed in small intestinal epithelial organoids. TWEAK stimulation increased mRNA expression by approximately 1.56-fold and reduced mRNA expression to approximately 66% of control, without markedly affecting epithelial proliferation or stem cell markers. TWEAK did not significantly alter the PAS-positive mucin area or AB-PAS-defined mucin composition, whereas PGM34 staining showed a non-significant tendency to increase. TNF treatment reproduced some of the TWEAK-associated changes, including reduced mRNA expression and alterations in mucin-associated parameters, suggesting that TNF may contribute to some of the epithelial responses associated with TWEAK treatment. Treatment with an anti-TNF neutralizing antibody modified several TWEAK-associated responses, including changes in epithelial-associated gene expression and mucin-associated staining parameters. These findings suggest that TWEAK treatment is associated with goblet cell-related mucin responses in mouse small intestinal epithelial organoids, with possible involvement of TNF signaling. - Source: PubMed
Publication date: 2026/08/26
Tamaki ShunKono MasayukiArikawa SakuraHigashi YuiMaekawa TatsunoriHara YusukeTsujimoto TaizoKawakami FumitakaImai MotokiKurosaki YoshifumiNaito ShokichiIshii NaohitoIchikawa TakafumiKawashima Rei - Mitochondrial dysfunction is an important cause of sarcopenia, and TWEAK/Fn14, as one of the major muscle wasting cytokines, its role in the development of sarcopenia by regulating mitochondrial biogenesis remains unclear. Expression of TWEAK in old and young mice was both detected. TWEAK was silenced in C2C12 myocytes using lentiviral vectors. Immunofluorescence, western blot, real-time polymerase chain reaction (RT-PCR), and ELISA were enrolled to analyze the effects of TWEAK on myotube size, mitochondrial content, mitochondrial ROS, and inflammatory factors. Additionally, aged mice received two injections of AAV9 vectors at 15 and 17 months of age. Upon reaching 18 months of age, the effects of TWEAK knockdown on grip strength, muscle mass, and gastrocnemius muscle indices were evaluated. TWEAK/Fn14 expression was significantly increased in old mice (p < 0.001). Compared with young controls, old mice exhibited a significant decrease in grip strength (p < 0.001) and a significant increase in lean mass (p < 0.05), whereas no significant difference was observed in fat content. In DEX-treated C2C12 myotubes, TWEAK knockdown significantly increased myotube diameter, enhanced ATP content and mitochondrial quantity, upregulated protein expression of SIRT1, PGC-1α, and p-AMPK, and inhibited mitochondrial ROS, Ca levels, p-p38 expression, and the secretion of inflammatory cytokines (TNF-α, IL-1β, IL-6, and iNOS). In aged mice, TWEAK knockdown did not significantly alter forelimb grip strength or lean mass, but significantly increased fat mass (p < 0.05). Mechanistically, TWEAK knockdown promoted AMPK signaling, inhibited p38 MAPK activation, enhanced mitochondrial biogenesis, and reduced serum levels of IL-1β, IL-6, and iNOS (p < 0.05), whereas serum TNF-α levels showed no significant difference. TWEAK knockdown attenuates age-related skeletal muscle mass loss and improves mitochondrial biogenesis in skeletal muscle, accompanied by modulated inflammatory factor release and altered AMPK-p38 MAPK signaling activity. However, no significant improvement in forelimb grip strength was observed in the in vivo experiment. These findings indicate that TWEAK suppression may represent a promising strategy for preserving muscle mass and metabolic homeostasis during aging, though its capacity to fully restore functional capacity requires further investigation. - Source: PubMed
Publication date: 2026/08/14
Maimaitiwusiman ZhuoyaXuekelati SaiyareWang AnyanAiriken NadilaXu YanbinGuo ShukeYang YiningWang Hongmei - BACKGROUNDElucidating immune signals through well-defined cohorts of pediatric acute pancreatitis (AP) and chronic pancreatitis (CP) patients is critical. This study aimed to evaluate plasma chemokine and cytokine levels in pediatric participants with CP, compared with AP and healthy controls (HCs), to identify unique biomarkers of CP.METHODSIndividuals were identified from a prospectively collected pediatric cohort (n = 146). Immunoproteins (n = 247) were measured using the NULISAseq platform on samples from individuals with CP (n = 71), AP (n = 55), and HCs (n = 20).RESULTSThe measured analytes showed separation among the 3 groups (R2 = 0.13, P < 0.001). In the CP group, TRANCE, TWEAK, FLT-1, HGF, and TRAIL were increased when compared with HC and AP patients (FDR-corrected P <0.05). A multivariable logistic regression model including all 5 proteins provided an AUC of 0.94 (0.93-0.96) for differentiating samples from CP versus AP or HC samples. In the AP group, CRP, IL-6, CD3E, ENRAGE, and MIF were elevated compared with HCs, while FGF-2, TAFA-5, IL-33, TRANCE, and CXCL12 were downregulated in the same acute time period (FDR-corrected P < 0.05). In the 21 patients with AP for whom follow-up samples were obtained, there was a notable decrease in sequential expression of IL-6 and CRP over 12 months and increased expression of CCL25, TAFA-5, and TRANCE proteins. Additionally, TRANCE was expressed on CP pancreatic tissue.CONCLUSIONSTRANCE was increased in pediatric patients with CP and decreased in those with AP during a flare. Future studies are needed to investigate the role of TRANCE and other analytes in the pathogenesis of CP. - Source: PubMed
Publication date: 2026/08/24
Farrell Peter RLee BomiAhmed FaizanMoreno-Fernandez Maria EDixit AjayGurria Juan PabloOllberding Nicholas JDuan QingGarlapally VineetChristian PhoebeHusain Sohail ZAbu-El-Haija Maisam - The immunopathogenesis of clade IIb monkeypox virus (MPXV) infection and its relationship with clinical severity remain poorly defined. We characterized cytokine responses in acute and convalescent mpox to delineate inflammatory profiles. - Source: PubMed
Publication date: 2026/07/23
Byrne JoanneSaini GurvinGarcia-Leon AlejandroAlalwan DanaLanday AlanNguyen Liem Binh LuongSavinelli StefanoO'Broin CathalHorgan MaryKelly ChristineCotter AoifeSadlier Corinnade Barra EoghanO'Halloran Jane AGautier VirginieMallon Patrick W GFeeney Eoin R - To explore the causal relationships between human inflammatory proteins and hypertrophic scars (HS) and keloids. This study was conducted based on bidirectional two-sample Mendelian randomization (MR) analysis. Data of human inflammatory proteins, HS, and keloids were acquired from genome-wide association study database. The inverse variance weighted (IVW) method was adopted to evaluate the causal relationships between 91 kinds of human inflammatory proteins and HS and keloids, i.e., a forward MR analysis. For the above associations, Cochran's Q test was used to assess heterogeneity, MR-Egger regression and MR-PRESSO outlier tests were performed to evaluate horizontal pleiotropy, and the leave-one-out method was applied to analyze the robustness of the results. The IVW method was also used to evaluate whether there was a reverse causal relationship between HS, keloids and inflammatory proteins screened out by aforementioned forward MR analysis. CD6, leukemia inhibitory factor (LIF), tumor necrosis factor ligand superfamily member 12 (TNFSF12), programmed death-ligand 1 (PD-L1), interleukin-17C (IL-17C), LIF receptor (LIFR), osteoprotegerin (OPG), and fibroblast growth factor 23 (FGF23) had significant causal relationships with HS (with s of 1.365, 0.506, 1.567, 1.683, 0.621, 1.375, 0.623, and 0.553, respectively, 95% s of 1.100-1.693, 0.289-0.887, 1.081-2.273, 1.090-2.599, 0.408-0.947, 1.025-1.845, 0.402-0.966, and 0.315-0.971, respectively, <0.05). Among them, CD6, TNFSF12, PD-L1, and LIFR were risk factors for HS, while LIF, IL-17C, OPG, and FGF23 were protective factors for HS. CD5, IL-10 receptor subunit alpha (IL-10RA), IL-5, LIF, and OPG had significant causal relationships with keloids (with s of 0.744, 1.303, 0.686, 0.603, and 0.715, respectively, 95% s of 0.573-0.965, 1.024-1.660, 0.472-0.996, 0.431-0.842, and 0.553-0.924, respectively, <0.05). Among them, IL-10RA was a risk factor for keloids, whereas CD5, IL-5, LIF, and OPG were protective factors for keloids. No significant heterogeneity or horizontal pleiotropy was observed in the above associations (>0.05), and the robustness of the results was not driven by any single nucleotide polymorphism. Significant reverse causal relationships existed between HS and TNFSF12 and LIFR of the 8 inflammatory proteins which had significant causal relationships with HS screened out by aforementioned forward MR analysis (with s of 0.972 and 0.968, respectively, 95% s of 0.949-0.997 and 0.942-0.994, respectively, <0.05). No reverse causal relationship was found between keloids and the 5 inflammatory proteins which had significant causal relationships with keloids screened out by aforementioned forward MR analysis (>0.05). CD6, TNFSF12, PD-L1, and LIFR may increase the risk of HS, while LIF, IL-17C, OPG, and FGF23 may decrease the risk of HS. IL-10RA may increase the risk of keloids, while CD5, IL-5, LIF, and OPG may decrease the risk of keloids. - Source: PubMed
Wang S SXiao KXiao H THan D WZhang JWang LLi Y C