Investigation for anti-renal fibrotic effects of lipid-binding proteins and lipid-activated nuclear receptors and search for new therapeutic reagents

在人近端肾小管上皮细胞和肾小球系膜细胞中证实了过氧化物酶体增殖物激活受体-δ和γ的存在和活性，炎症损伤主要针对肾损伤的进展。血管紧张素II受体阻滞剂替米沙坦被证明具有PPAR-δ和γ诱导的转录活性，并增加其靶基因如脂肪酸结合蛋白和肝X受体的表达。替米沙坦还可降低单核细胞趋化蛋白-1(MCP-1)的基因表达。在人肝型FABP高表达的永生化近端肾小管上皮细胞系中，小鼠PPAR-δ表达上调，MCP-1表达下调。这些结果表明，一些可能影响PPAR和FABP功能和动态的生物活性分子是治疗慢性肾脏疾病的新药物的候选药物。

Presence and activities of peroxisome proliferator-activated receptor(PPAR)-δandγwere confirmed in human proximal renal tubular epithelial cells and mesangial cells which inflammatory insults targeted mainly during progression of renal injury. An angiotensin II receptor blocker, telmisartan was shown to have PPAR-δandγ-induced transcriptional activities and increase expression of their target genes such as fatty acid-binding protein(FABP) and liver X receptor. Telmisartan also decreased gene expression of monocyte chemoattractant protein-1(MCP-1). In the mouse immortalized proximal renal tubular cell line with over-expression of human liver-type FABP, a putative transporter of PPAR ligands, mouse PPAR-δwas up-regulated and MCP-1 down-regulated. These results suggest that some bioactive molecules with a potential to affect function and dynamism of PPAR and FABP are candidates of new therapeutic reagents for chronic kidney disease.