成長期における食餌性リンによるα-klotho発現制御

Inorganic phosphate (Pi) is an essential nutrient for maintaining various biological functions, particularly during growth periods. Excess intake of dietary Pi increases the secretion of fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) to maintain plasma Pi levels. FGF23 is a potent phosphaturic factor that binds to the α-klotho/FGFR complex in the kidney to promote excretion of Pi into the urine. In addition, excess intake of dietary Pi decreases renal α-klotho expression. Down-regulation or lack of α-klotho induces a premature aging-like phenotype, resulting from hyperphosphatemia, and leading to conditions such as ectopic calcification and osteoporosis. However, it remains unclear what effects dietary Pi has on α-klotho expression at different life stages, especially during growth periods. To investigate this, we used C57BL/6J mice in two life stages during growing period. Weaned (3 weeks old) and periadolescent (7 weeks old) were randomly divided into seven experimental groups and fed with 0.02, 0.3, 0.6, 0.9, 1.2, 1.5, or 1.8% Pi diets for 7 days. As a result, elevated plasma Pi and FGF23 levels and decreased renal α-klotho expression were observed in weaned mice fed with a high Pi diet. In addition, a high Pi diet clearly induced renal calcification in the weaned mice. However, in the periadolescent group, renal calcification was not observed, even in the 1.8% Pi diet group. The present study indicates that a high Pi diet in weaned mice has much greater adverse effects on renal α-klotho expression and pathogenesis of renal calcification compared with periadolescent mice

Hepatitis C Virus Infection Suppresses the Interferon Response in the Liver of the Human Hepatocyte Chimeric Mouse

BACKGROUND AND AIMS: Recent studies indicate that hepatitis C virus (HCV) can modulate the expression of various genes including those involved in interferon signaling, and up-regulation of interferon-stimulated genes by HCV was reported to be strongly associated with treatment outcome. To expand our understanding of the molecular mechanism underlying treatment resistance, we analyzed the direct effects of interferon and/or HCV infection under immunodeficient conditions using cDNA microarray analysis of human hepatocyte chimeric mice. METHODS: Human serum containing HCV genotype 1b was injected into human hepatocyte chimeric mice. IFN-α was administered 8 weeks after inoculation, and 6 hours later human hepatocytes in the mouse livers were collected for microarray analysis. RESULTS: HCV infection induced a more than 3-fold change in the expression of 181 genes, especially genes related to Organismal Injury and Abnormalities, such as fibrosis or injury of the liver (P = 5.90E-16∼3.66E-03). IFN administration induced more than 3-fold up-regulation in the expression of 152 genes. Marked induction was observed in the anti-fibrotic chemokines such as CXCL9, suggesting that IFN treatment might lead not only to HCV eradication but also prevention and repair of liver fibrosis. HCV infection appeared to suppress interferon signaling via significant reduction in interferon-induced gene expression in several genes of the IFN signaling pathway, including Mx1, STAT1, and several members of the CXCL and IFI families (P = 6.0E-12). Genes associated with Antimicrobial Response and Inflammatory Response were also significantly repressed (P = 5.22×10(-10)∼1.95×10(-2)). CONCLUSIONS: These results provide molecular insights into possible mechanisms used by HCV to evade innate immune responses, as well as novel therapeutic targets and a potential new indication for interferon therapy

Evaluation of yield and tuber functionality in short-term cultivation of Chinese artichoke using propagated cuttings

The Chinese artichoke (Stachys affinis) is a vegetable that is also used as a medicinal plant. There are two major problems in growing Chinese artichoke. One is the re-infection of viruses when propagating virus-free seed tubers, and the other is too long a cultivation period before harvest. The application of rooted cuttings technology to tuber production could allow virus-free cuttings to be propagated annually and planted at any time of the year. We showed that 100% of the cuttings were rooted within 14 days when the electrical conductivity of the nutrient solution was less than 0.42 dS·m−1. There was no significant difference in yield or tuber size between tubers derived from rooted cuttings and those derived from seed tubers (the conventional method of cultivation). Although the yield of rooted cuttings planted in July, August and September decreased slightly with delayed planting time, tubers of marketable size were harvested even when planted in September, the shortest growing season. The stachyose content, polyphenol content and antioxidant activity of the tubers did not differ significantly with planting time. In conclusion, short-term cultivation of Chinese artichoke using rooted cuttings is feasible for commercial tuber production.</p

The effect of HCV infection on biological functions by category.

<p>The effect of HCV infection on biological functions by category.</p

The top 6 genes down-regulated with IFN treatment.

<p>The top 6 genes down-regulated with IFN treatment.</p

Hierarchical clustering analysis of 181 genes associated with HCV infection.

<p>To analyze the influence of HCV infection on human hepatocytes, clustering analysis on gene expression was performed between Group A (without HCV infection; 4 columns on the left side) and Group C (with HCV infection; 3 columns on the right side). 157 genes were up-regulated following HCV infection, including interferon-stimulated genes (ISGs) such as <i>MX1</i> and genes in the <i>CXCL</i> and <i>IFI</i> families, and 24 genes were down-regulated, including <i>ME1</i> and <i>HMGCS1</i>.</p