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出てました

共同研究をしている福井大学の腎臓内科の先生方の論文がon lineになりました。
季先生おめでとうございました。

Hypoxia reduces the expression and anti-inflammatory effects of peroxisome proliferator-activated receptor-{gamma} in human proximal renal tubular cells -- Li et al., 10.1093/ndt/gfl766 -- Nephrology Dialysis Transplantation


Abstract
Background. Peroxisome proliferator-activated receptor (PPAR)- may counteract tissue fibrosis via its anti-inflammatory actions, while hypoxia, a new pro-fibrotic factor, reportedly modifies PPAR- expression. However, the effects of hypoxia on the expression and anti-inflammatory actions of PPAR- have yet remained to be clarified in renal tubular cells.
Methods. Confluent human proximal renal tubular epithelial cells (HPTECs) were exposed to hypoxia (1% O2) and/or TNF- at 10 ng/ml for up to 48 h. The cells were incubated with PPAR- agonists, 15d-PGJ2 or pioglitazone, for 30 min before stimulation. Precise amounts of PPAR- and MCP-1 mRNA and protein were measured by TaqMan quantitative PCR and immunoblot or ELISA, respectively.
Results. A cDNA array analysis identified PPAR- as one of the hypoxia-affected genes in HPTECs. Hypoxia reduced mRNA levels of PPAR- at 24 and 48 h and protein levels at 6 and 48 h. Knockout of hypoxia-inducible factor-1 (HIF-1) with its dominant negative form did not block the hypoxia-induced reduction in PPAR- expression. PPAR-'s activation with 15d-PGJ2 or pioglitazone reduced basal and TNF--stimulated MCP-1 expression at mRNA and protein levels at 24 h under normoxia. MCP-1 reduction rates at basal mRNA and protein levels were slightly but significantly lower during hypoxia than normoxia (9 vs 69% and 36 vs 42%, respectively, for 15d-PGJ2, and 0 vs 34% and 12 vs 21%, respectively, for pioglitazone). Finally, a specific inhibitor for PPAR-, GW9662, weakened the MCP-1-decreasing effect of 15d-PGJ2 by about 30%, under basal conditions, while it abolished the effect of pioglitazone almost completely.
Conclusions. Hypoxia-induced loss of function of PPAR- reduces anti-inflammatory effects of PPAR- activation, possibly modulating inflammatory responses in the diseased kidney.
Keywords: HIF-1; human proximal tubular cells; hypoxia, MCP-1; PPAR; TNF-

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2007年01月27日 19:03に投稿されたエントリのページです。

ひとつ前の投稿は「今週の一押し2007-#5:""香水―ある人殺しの物語"」です。

次の投稿は「今週の一押し2007-#6:"大学病院改革”」です。

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