Browsing by Subject "TXNIP"

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    1,25-Dihydroxyvitamin D3 mitigates high glucose-induced oxidative stress, inflammation, and extracellular matrix accumulation in glomerular mesangial cells via the ROS/TXNIP/NLRP3 pathway
    (2026) Bo Chen; Chunjiang Zhang; Lin Jia; Xingyu Yao; Gang Liu; Qingyue Meng; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
    ackground. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is a physiologically active form of vitamin D. Our study investigated the renoprotective functions of 1,25(OH)2D3 in diabetic nephropathy (DN) progression and its underlying mechanism targeting the ROS/TXNIP/NLRP3 inflammasome pathway. Methods. DN was induced in Wistar rats via high-fat diet (4 weeks) and streptozotocin injection (30 mg/kg, i.p.); hyperglycemic rats were randomized into DN and DN + 1,25(OH)2D3 (16 μg/kg, 12 weeks) groups. Rat mesangial HBZY-1 cells were maintained under normal glucose (5.5 mM), high glucose (25 mM), high glucose plus 1,25(OH)2D3 (1-50 nM), or high glucose plus N acetylcysteine (NAC, 10 mM). Cell viability was assessed by the CCK-8 assay. Oxidative stress parameters (ROS via DCFH-DA fluorescence, MDA content, SOD activity) and pyroptosis markers (LDH release, PI/Hoechst 33342 nuclear staining) were quantified. Renal histopathology was performed using PAS and Masson trichrome staining. Biochemical analyses included serum creatinine, urea nitrogen, and 24h urinary protein quantification. Molecular profiling encompassed ELISA (IL-1β, IL-6, TNF-α, IL-18, fibronectin, collagen IV), RT-qPCR (NOX2, NOX4, NLRP3, ASC), western blotting (TXNIP, NLRP3, ASC, caspase-1, IL-1β, IL-18, collagen IV, fibronectin, laminin), and TXNIP immunofluorescence. Results. 1,25(OH)2D3 significantly attenuated high glucose-induced pathological alterations in HBZY-1 cells, including ROS overproduction, TXNIP upregulation, NLRP3 inflammasome activation, oxidative stress, inflammation, extracellular matrix (ECM) deposition, and pyroptotic cell death. Consistently, 1,25(OH)2D3 suppressed ROS/TXNIP/ NLRP3/caspase-1 signaling, ameliorated renal dysfunction, and mitigated histopathological damage in DN rats. Conclusion. 1,25(OH)2D3 confers renoprotection in DN by inhibiting the ROS/TXNIP/NLRP3 inflamma some axis, thereby suppressing oxidative stress, inflammatory cytokine production, ECM accumulation, and pyroptotic cell death in glomerular mesangial cells and renal tissues.
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    Inflammatory risk factors and pathologies promoting Alzheimer’s disease progression: is RAGE the key?
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Matrone, Carmela; Djellou, Mehdi; Taglialatela, Giulio; Perrone, Lorena
    Epidemiological studies reveal growing evidence that most cases of Alzheimer’s Disease (AD) likely involve a combination of genetic and environmental risk factors. Identifying and validating these risk factors remains one of the most critical scientific challenges. Several diseases appear to have strong implications for neurodegeneration leading to dementia. This risk encompasses different forms of cardiovascular disease, carotid atherosclerosis, history of hypertension or high cholesterol, Type II diabetes, stroke or transient ischemic attack and brain trauma. However, the molecular pathways that are common and central in the progression of these diseases and AD are not yet elucidated. Unveiling these critical mechanisms at the molecular level is necessary for the development of therapeutic strategies aimed at preventing AD progression. The Receptor for Advanced Glycation Endproducts (RAGE) plays a key role in all the diseases that represent a risk for AD. RAGE-mediated signaling also contributes to neurodegeneration in AD, suggesting that it may mediate the effect of risk factors in promoting AD. We will summarize the current knowledge on the role of RAGE in pathologies promoting AD and in AD progression. We will also provide evidence showing the relevance of RAGEinduced inflammation as a risk pathway that is implicated in AD pathophysiology.