Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans
Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans
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DOI：
10.1152/ajprenal.1997.273.6.f1013
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发表时间：
1997-12-01
影响因子：
4.2
通讯作者：
Breyer, MD
中科院分区：
文献类型：
--
作者：
Guan, YF;Zhang, YH;Breyer, MD
过氧化物酶体增殖物激活受体(PPAR)是配体激活的转录因子核受体超家族的成员。PPAR调节与脂代谢有关的基因的表达。8(S)-羟基二十碳四烯酸(8-S-HETE)、白三烯B-4(LTB_4)和降脂贝特类激活PPARα，而PPARγ则由前列腺素代谢产物激活。本研究检测了兔和人PPARα、β/β和γmRNAs在肾内和组织中的分布。核酸酶保护显示，PPARα主要分布在肝脏、心脏和肾脏，而PPARγ是一种可能的脂肪特异性转录因子，在白色脂肪组织、膀胱和回肠中占优势，其次是肾脏和脾。PPARβ/Delta在多个组织中的表达水平较低。肾脏原位杂交结果显示，PPARα在兔和人的近端肾小管和髓质厚的升支均有表达。PPAR-γ仅在髓质集合管和乳头状尿路上皮细胞中表达。免疫印迹证实PPAR-γ蛋白在新鲜分离的内髓集合管中表达。在兔和人的输尿管和膀胱中，所有PPAR的mRNAs都有表达，但PPARγ的表达最强。PPAR亚型的这种不同的分布对尿路上皮细胞中脂质激活基因的转录具有重要的意义。
Peroxisome proliferator-activated receptors (PPARs, alpha, beta/delta, and gamma) are members of the nuclear receptor superfamily of ligand-activated transcription factors. PPARs regulate the expression of genes involved in lipid metabolism. 8(S)-hydroxyeicosatetraenoic acid (8-S-HETE), leukotriene B-4 (LTB4), and hypolipidemic fibrates activate PPAR alpha, whereas PPAR gamma is activated by prostaglandin metabolites. The present studies examined the intrarenal and tissue distribution of rabbit and human PPAR alpha, -beta/delta, and -gamma mRNAs. Nuclease protection showed PPAR alpha predominated in liver, heart, and kidney, whereas PPAR gamma, a putative adipose-specific transcription factor, was in white adipose tissue, bladder, and ileum, followed by kidney and spleen. Lower expression levels of PPAR beta/delta were observed in several tissues. In situ hybridization of kidney showed PPAR alpha mRNA predominated in proximal tubules and medullary thick ascending limbs of both rabbit and human. PPAR gamma was exclusively expressed in medullary collecting duct and papillary urothelium. Immunoblot confirmed the expression of PPAR gamma protein in freshly isolated inner medullary collecting ducts. mRNAs for all the PPARs were expressed in the ureter and bladder in both rabbit and human, but PPAR gamma, expression was greatest. This distinct distribution of PPAR isoforms has important implications for lipid-activated gene transcription in urinary epithelia.