Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney
Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney
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DOI：
10.1152/ajprenal.1999.277.6.f966
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发表时间：
1999-12-01
影响因子：
4.2
通讯作者：
Briggs, JP
中科院分区：
文献类型：
--
作者：
Yang, TX;Michele, DE;Briggs, JP
发现15-脱氧-δ（12，14）-前列腺素J（2）（15 d-PGJ（2））是过氧化物酶体增殖物激活受体（PPAR）的γ-亚型的配体，提示了通过野牡丹素的核信号传导。进行了研究，以确定肾单位定位的过氧化物酶体增殖物激活受体亚型及其异二聚体的合作伙伴，类维生素A X受体（RXR），并评估该系统在肾脏中的功能。通过RT-PCR测定，发现PPAR α mRNA主要存在于皮质中，并进一步定位于近曲小管（PCT）; PPAR γ在肾髓质中丰富，定位于内髓集合管（IMCD）和肾髓质间质细胞（RMIC）; PPAR β，PPAR的普遍存在形式，在检查的所有肾单位节段中丰富。RXR α定位于PCT和IMCD，而RXR β在几乎所有检查的肾单位节段中表达。非诺贝特组大鼠肾皮质中的酰基辅酶A合酶（ACS）（一种已知的PPAR靶基因）mRNA表达受到刺激，但曲格列酮组大鼠的皮质或髓质内的表达没有显著改变。在培养的RMIC细胞中，曲格列酮和15 d-PGJ（2）均显著抑制细胞增殖，并通过诱导细胞突起形成显著改变细胞形状。我们的结论是，过氧化物酶体增殖物激活受体和RXR亚型表达的肾单位段的具体方式，表明不同的功能，与过氧化物酶体增殖物激活受体α参与能量代谢，通过调节ACS在PCT和与过氧化物酶体增殖物激活受体γ参与调节RMIC的生长和分化。
The discovery that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a ligand for the gamma-isoform of peroxisome proliferator-activated receptor (PPAR) suggests nuclear signaling by prostaglandins. Studies were undertaken to determine the nephron localization of PPAR isoforms and their heterodimer partners, retinoid X receptors (RXR), and to evaluate the function of this system in the kidney. PPAR alpha mRNA, determined by RT-PCR, was found predominately in cortex and further localized to proximal convoluted tubule (PCT); PPAR gamma was abundant in renal inner medulla, localized to inner medullary collecting duct (IMCD) and renal medullary interstitial cells (RMIC); PPAR beta, the ubiquitous form of PPAR, was abundant in all nephron segments examined. RXR alpha was localized to PCT and IMCD, whereas RXR beta was expressed in almost all nephron segments examined. mRNA expression of acyl-CoA synthase (ACS), a known PPAR target gene, was stimulated in renal cortex of rats fed with fenofibrate, but the expression was not significantly altered in either cortex or inner medulla of rats fed with troglitazone. In cultured RMIC cells, both troglitazone and 15d-PGJ(2) significantly inhibited cell proliferation and dramatically altered cell shape by induction of cell process formation. We conclude that PPAR and RXR isoforms are expressed in a nephron segment-specific manner, suggesting distinct functions, with PPAR alpha being involved in energy metabolism through regulating ACS in PCT and with PPAR gamma being involved in modulating RMIC growth and differentiation.