一氧化氮合酶
内分泌学
信号转导
内科学
转化生长因子
小干扰RNA
化学
一氧化氮
分子生物学
细胞生物学
生物
医学
转染
生物化学
基因
作者
Ellen Dreieicher,Karl‐Friedrich Beck,Sandra Lazaroski,Meike Boosen,Wasiliki Tsalastra-Greul,Martina Beck,Ingrid Fleming,Liliana Schaefer,Josef Pfeilschifter
出处
期刊:Journal of The American Society of Nephrology
日期:2009-09-01
卷期号:20 (9): 1963-1974
被引量:22
标识
DOI:10.1681/asn.2008060653
摘要
Cytokines and nitric oxide (NO) stimulate rat mesangial cells to synthesize and secrete inflammatory mediators. To understand better the signaling pathways that contribute to this response, we exposed rat mesangial cells to the prototypic inflammatory cytokine IL-1β and analyzed the changes in the pattern of gene expression. IL-1β downregulated the gene encoding the matricellular glycoprotein secreted modular calcium-binding protein 1 (SMOC-1) in mesangial cells. Inflammatory cytokines attenuated SMOC-1 mRNA and protein expression through endogenous production of NO, which activated the soluble guanylyl cyclase. Silencing SMOC-1 expression with small interfering RNA decreased the formation of TGF-β, reduced SMAD binding to DNA, and decreased mRNA expression of genes regulated by TGF-β. In a rat model of anti–Thy-1 glomerulonephritis, glomerular SMOC-1 mRNA and protein decreased and inducible NO synthase expression increased simultaneously. Treatment of nephritic rats with the inducible NO synthase–specific inhibitor l-N6-(1-iminoethyl)-lysine prevented SMOC-1 downregulation. In summary, these data suggest that NO attenuates SMOC-1 expression in acute glomerular inflammation, thereby limiting TGF-β–mediated profibrotic signaling.
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