Journal: Acta Pharmacologica Sinica

Article Title: Involvement of endoplasmic reticulum stress in angiotensin II-induced NLRP3 inflammasome activation in human renal proximal tubular cells in vitro

doi: 10.1038/aps.2015.21

Figure Lengend Snippet: Angiotensin II induced inflammasome activation in tubular epithelial cells. (A) Real-time PCR and (C, E, and G) western blot analysis show that the mRNA and protein expression of caspase-1, IL-1β, and IL-18 were increased after treatment with different amounts (0, 10, 100, or 1000 nmol/L) of angiotensin II for 12 h in serum-free medium. (B) Real-time PCR and (D, F, and H) western blot analysis indicate that the mRNA and protein expression of caspase-1, IL-1β, and IL-18 were increased after treatment with 100 nmol/L angiotensin II for various time periods (0, 6, 12, or 24 h) in serum-free medium. β-Actin served as an internal control gene. The results represent the mean±SD from four experiments. bP<0.05 vs control.

Article Snippet: Human kidney proximal epithelial cells (HK-2) were purchased from the China Center for Type Culture Collection (CCTCC).

Techniques: Activation Assay, Real-time Polymerase Chain Reaction, Western Blot, Expressing, Control

Journal: Frontiers in Immunology

Article Title: Vericiguat attenuates cyclosporine A-induced nephropathy by targeting the NF-κB/TGF-β1 axis: an integrated network pharmacology, Mendelian randomization, and experimental study

doi: 10.3389/fimmu.2025.1756582

Figure Lengend Snippet: Proposed molecular mechanism of cyclosporine A-induced renal injury and the protective role of vericiguat via the ROS/NF-κB/TGF-β1/Smad signaling axis. Cyclosporine A (CsA) enters renal tubular epithelial cells and induces mitochondrial dysfunction, leading to excessive reactive oxygen species (ROS) production. ROS activates the IKK complex, resulting in IκBα phosphorylation and degradation, followed by nuclear translocation of NF-κB p65 and transcription of pro-inflammatory cytokines (e.g., TNF-α and IL-6). Concurrently, ROS promotes TGF-β1 signaling through ALK5-mediated phosphorylation of Smad2/3, complex formation with Smad4, and suppression of Smad7. This drives epithelial–mesenchymal transition (EMT), extracellular matrix deposition, and renal fibrosis. Vericiguat, as an sGC stimulator, interferes with this vicious cycle by inhibiting both NF-κB activation and TGF-β1/Smad signaling, thereby exerting anti-inflammatory, anti-fibrotic, and antioxidant effects in CsA-induced chronic kidney disease (CKD). ROS, reactive oxygen species; IKK, IκB Kinase; IκBα, Inhibitor of Nuclear Factor Kappa B Alpha; NF-κB, Nuclear Factor Kappa B; TNF-α, Tumor Necrosis Factor Alpha; IL-6, Interleukin-6; TGF-β1, Transforming Growth Factor Beta 1; ALK5, Activin Receptor-Like Kinase 5; Smad, Mothers Against Decapentaplegic Homolog (from Drosophila ); α-SMA, Alpha-Smooth Muscle Actin; EMT, epithelial–mesenchymal transition; ECM, extracellular matrix.

Article Snippet: The human renal proximal tubular epithelial cell line (HK-2) was obtained from Procell (Wuhan, China) and authenticated by Short Tandem Repeat (STR) profiling.

Techniques: Phospho-proteomics, Translocation Assay, Activation Assay