Ask about this productRelated genes to: TXNIP antibody
- Gene:
- TXNIP NIH gene
- Name:
- thioredoxin interacting protein
- Previous symbol:
- -
- Synonyms:
- VDUP1, EST01027, HHCPA78, THIF, ARRDC6
- Chromosome:
- 1q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-12-12
- Date modifiied:
- 2016-10-05
Related products to: TXNIP antibody
Related articles to: TXNIP antibody
- Cardiovascular disease (CVDs) and atherosclerosis remain a major causes of morbidity and mortality worldwide. Endothelial dysfunction is a central driver of atherosclerosis, which is significantly accelerated in diabetes mellitus through hyperglycemia-induced oxidative stress, oxidized low-density lipoprotein (oxLDL) accumulation, and NLRP3 inflammasome activation. Phenolic acids, a class of plant-derived polyphenols, have gained attention as vasoprotective agents due to their antioxidant and anti-inflammatory properties. Among them, rosmarinic acid and salvianolic acid have gained attention, yet no previous review has systematically compared their distinct molecular mechanisms. This review addresses the gap by summarizing the pathophysiological mechanisms linking endothelial dysfunction to atherosclerotic progression and comparing how rosmarinic acid and salvianolic acid modulate oxidative stress, nitric oxide signaling, inflammatory responses, and NLRP3 inflammasome activation. Rosmarinic acid primarily exerts its effects through the p38 MAPK-FOXO1-TXNIP and AMPK/eNOS pathways, while salvianolic acid mainly acts via the PKM2/PKR and NF-ĸB/NLRP3 signaling pathways. Despite these findings, clinical evidence remains limited, primarily limited to Phase 1 pharmacokinetic studies and mixed-extract trials, leaving compound-specific efficacy in humans unverified. This review highlights these translational gaps and suggests prioritizing clinical trials of purified compounds, bioavailability optimization, and dose-standardization studies to advance rosmarinic acid and salvianolic acid toward clinical application in diabetic atherosclerosis. - Source: PubMed
Publication date: 2026/07/24
Won YaeramKim Hye Jung - Diabetic nephropathy (DN) is a chronic metabolic disorder characterized by hyperglycaemia-induced disruption of renal homeostasis. Emerging evidence suggests that the TRX/TXNIP axis mediates oxidative stress and inflammation in DN. However, its specific role in regulating ER-mitochondrial dysfunction and renal fibrosis remains unclear. Streptozotocin (STZ)-induced diabetic rats exhibited a progressive decline in body weight and increased feed consumption from the 6 week onward. These rats showed reduced renal antioxidant levels and elevated malondialdehyde (MDA) concentrations. Histopathological analysis revealed renal structural alterations, impaired kidney function, and increased accumulation of glycogen and type I collagen over time. Additionally, DN progression was associated with a gradual upregulation of TXNIP, α-SMA, and p-NF-κB, as demonstrated by immunohistochemistry. Immunoblot analysis revealed increased expression of TXNIP, COL-1, and TGF-β1, accompanied by decreased levels of TXN-2 and beclin-1. Silencing of TXNIP alleviated ER-mitochondrial dysfunction (GRP78 and DRP-1), reduced apoptosis (decreased cleaved caspase 3 and increased Bcl-2 levels), and suppressed fibrogenic markers (TGF-β1 and COL-1) in NRK-52E cells exposed to high glucose (HG). Furthermore, we performed integrated high-field 800 MHz Nuclear Magnetic Resonance (NMR) based metabolomics analysis of renal tissues to identify metabolic signatures associated with DN progression. The findings revealed time-dependent accumulation of branched-chain amino acids and decreased myo-inositol levels at 12 week during the progression of DN. Collectively, these findings suggest that the TRX/TXNIP axis contributes to renal fibrosis through ER-mitochondrial cross-talk and metabolic alterations during the development of DN. - Source: PubMed
Publication date: 2026/08/11
Yadav Karan SinghSingh GurvinderIshteyaque SharmeenVerma ShobhitVerma SmritiYadav ManishaSrivastava Anurag KumarKumar DineshMugale Madhav Nilakanth - Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia and progressive multi-organ complications driven by oxidative stress, inflammation, and metabolic dysfunction. Accumulating experimental evidence identifies the thioredoxin-interacting protein (TXNIP)-NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome axis as a critical molecular link between hyperglycemia-induced oxidative stress and inflammatory cell death, although its therapeutic modulation in diabetes remains under active investigation. Activation of TXNIP promotes assembly of the NLRP3 inflammasome, leading to caspase-1 activation, maturation of interleukin (IL)-1β and IL-18, and subsequent pyroptosis. This pathway has been increasingly implicated in the pathogenesis of diabetic complications, including nephropathy, retinopathy, neuropathy, cardiomyopathy, and diabetic osteopathy. Therefore, therapeutic strategies targeting upstream regulators of inflammasome activation have gained considerable attention. Allopurinol, a xanthine oxidase (XO) inhibitor traditionally used for the management of gout and hyperuricemia, possesses well-established antioxidant and anti-inflammatory properties that extend beyond urate lowering. By inhibiting XO-mediated reactive oxygen species (ROS) generation, allopurinol attenuates oxidative stress, improves endothelial function, and modulates inflammatory signaling pathways associated with diabetic tissue injury. Emerging experimental evidence suggests that suppression of XO-derived oxidative stress may indirectly influence TXNIP-NLRP3 inflammasome activation and downstream pyroptotic pathways, although whether allopurinol directly modulates this pathway has not yet been conclusively established. This review critically examines the mechanistic relationship between XO-derived oxidative stress, TXNIP-NLRP3 inflammasome signaling, and pyroptosis in diabetes. We distinguish experimentally validated mechanisms from biologically plausible hypotheses and critically evaluate current evidence supporting the potential role of allopurinol as an upstream modulator of inflammasome activation, with particular emphasis on the emerging and underexplored field of diabetic osteopathy. - Source: PubMed
Publication date: 2026/08/10
Qamar FaizParveen RamshaVaseem MohdAhmad TufailVohora DivyaSharma Manju - Food-derived bioactive components play a crucial role in the prevention of cardiovascular diseases. Daidzein (DAI), a soy isoflavone, possesses notable cardioprotective potential; however, its precise role in nicotine-induced atherosclerosis (AS) and its underlying mechanisms remain unclear. This study explored whether DAI protects against AS by modulating macrophage pyroptosis and lipid metabolism via redox-sensitive signaling pathways. In human acute monocytic leukemia cell line (THP-1)-derived macrophages, DAI alleviated nicotine-induced pyroptosis, as evidenced by the downregulation of NOD-like receptor family pyrin domain-containing 3 (NLRP3), ASC, cleaved caspase-1, and gasdermin D (GSDMD)-N, accompanied by reduced secretion of interleukin (IL)-1β, IL-6, and IL-18, and decreased lactate dehydrogenase (LDH) release and caspase-1 activity. DAI also enhanced (7-nitrobenz-2-oxa-1,3-diazole)-cholesterol (NBD)-cholesterol efflux, suppressed DiI-labeled oxidized low-density lipoprotein (DiI-ox-LDL) uptake, and mitigated intracellular lipid droplet accumulation. Mechanistically, silencing nuclear factor erythroid 2-related factor 2 (Nrf2), inducing reactive oxygen species (ROS), or overexpressing thioredoxin-interacting protein (TXNIP) abolished the protective effects of DAI, confirming the involvement of the Nrf2/ROS/TXNIP pathway. In nicotine-exposed apolipoprotein E-deficient (apoE) mice, DAI upregulated vascular Nrf2, downregulated TXNIP and pyroptosis-related proteins, improved plasma lipid profiles, alleviated systemic inflammation, and reduced aortic plaque formation, with no obvious adverse effects observed under the experimental conditions used. Collectively, DAI attenuated macrophage pyroptosis and lipid accumulation via the Nrf2/ROS/TXNIP pathway, thereby mitigating nicotine-induced atherogenesis. These findings provide preclinical evidence for the potential of DAI as a food-derived bioactive compound for smoking-related AS. - Source: PubMed
Xu Xiao-DanRen KunLiu XianWang Hui-HuiLan Xin-YuZhu LinMa Meng-QingLuo Wen-Wu - Regular engagement in physical exercise has been recognized as a formidable non-pharmacological intervention aimed at mitigating age-associated neuroinflammation and neurodegenerative phenomena. A fundamental mechanism that underpins these advantageous effects pertains to the modulation of the NLRP3 inflammasome, which serves as a pivotal regulator of innate immune responses within microglial cells. The aging process is marked by a state of chronic low-grade inflammation, commonly referred to as "inflammaging," which is instigated by mitochondrial dysfunction, oxidative stress, and metabolic disturbances; these factors collectively facilitate the activation of NLRP3 and the subsequent secretion of pro-inflammatory cytokines, notably IL-1β. Contemporary research findings suggest that physical exercise diminishes NLRP3 inflammasome activation through various interrelated pathways. These pathways encompass the reduction of reactive oxygen species production, the inhibition of TXNIP-mediated assembly of the inflammasome, and the modulation of metabolites derived from the gut, such as trimethylamine N-oxide. In addition, factors circulating as a result of exercise, which include irisin and meteorin-like protein, play a significant role in promoting systemic and central anti-inflammatory responses, thereby impacting the functional dynamics of microglia. In experimental paradigms investigating the phenomena of aging and neurodegenerative disorders (NDDs), notably Alzheimer's and Parkinson's diseases, physical activity has been shown to diminish amyloid accumulation, tau pathology, and microglial activation, primarily through the attenuation of NLRP3 signaling pathways. Collectively, these observations underscore the role of exercise as a pivotal regulator of neuroimmune equilibrium, thereby providing mechanistic elucidation of its potential therapeutic efficacy in alleviating inflammaging and decelerating the progression of NDDs. - Source: PubMed
Publication date: 2026/08/06
Zhang Yanxiao