This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

V infection group than in no infection group,while positive rate of other autoantibodies was not statistically different between the two groups.Conclusion Renal EBV infection may involve in the pathogenesis of LN by inducing the production of anti-Sm-Ab.

Aim To investigate the effects of Panax Notoginsenosides(PNS) on the gene expression and protein excretion of TGF-?_1 and CTGF of human renal tubular epithelial cell induced by uremic serum in vitro.Methods Forty sera from CRF patients and twenty sera from healthy volunteers were collected,gently mixed,inactived and separated respectively in steriled condition.HK-2 Cells were cultured in RPMI-1640 medium with 10% newborn calves serum and subcultured routinely.They were differentiated by phase contrast microscope and scanning electron microscope detection and cytokeratin18(CK-18) immunohistochemistry method.The protein levels of TGF-?_1 were examined by enzyme-linked immunoadsordent assay(ELISA).The protein levels of CTGF were examined by Western Bloting assay.The gene expression of TGF-?_1 and CTGF was detected by Semi-quantitative reverse trainscriptase polymerase chain reaction(RT-PCR).Results TGF-?_1 and CTGF gene expression and protein level were increased in 10% uremic serum groups compared with that of normal control group(P

Objective To investigate the effects of Free fatty acids (FFAs) on extracellular matrix(ECM) mRNA expression and secretion.Methods Rat glomerular mesangial cells(HBZY-1 cells) were cultured in vitro and stimulated with OA in different concentration.The expression of collagen Ⅳ(Col Ⅳ) and fibronectin (FN) and transforming growth factor-beta1(TGF-?_1) mRNA were measured by semi-quantitative RT-PCR.The levels of Col Ⅳ and FN in cultured supernatant were determined by ELISA.Results The mRNA expression of Col Ⅳ, FN and TGF-?_1 of 25、100、400 ?mol/L stimulated OA groups were 0.94?0.17、1.16?0.15、1.28?0.19 and 0.82?0.11、0.97?0.07、1.09?0.08 and 1.15? 0.07、1.24?0.06、1.36?0.05 respectively , which increased significantly compared with their control group(0.73?0.16、0.53?0.09、 0.96?0.11 P

10 000 D uremic toxin through promoting the gene and protein expression of CTGF in renal tubular epithelial cells in patients with chronic renal failure.

Objective:To study the effect of interleukin-18 on transdifferentiation in renal tubular epithelial cells(TECs).Methods:Human proximal tubular epithelial cell line(HK-2) was cultured in vitro.TECs were exposed to different concentrations(0,0.1,1,10 and 100 ng/ml) of IL-18 for 24,48 and 72 hours.At the end of each incubation,the expressions of the ?-SMA and TGF-?_1 mRNA were assessed by RT-PCR,the rate of ?-SMA expressing TECs was assessed by immunocytochemistry,and the expression of the ?-SMA protein was assessed by Western blotting.Results:(1)The expressions of ?-SMA and TGF-?_1 mRNA were increased significantly by a dose- and time-dependent manner when TECs were exposed to IL-18(P