Tissue-specific expression of PPAR mRNAs in diabetic rats and divergent effects of cilostazol.
Tissue-specific expression of PPAR mRNAs in diabetic rats and divergent effects of cilostazol.
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DOI：
10.1139/y08-043
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发表时间：
2008-06
影响因子：
2.1
通讯作者：
Fu-rong Wang;Ling Gao;B. Gong;Jianting Hu;Mei Li;Q. Guan;Jiajun Zhao
中科院分区：
文献类型：
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作者：
Fu-rong Wang;Ling Gao;B. Gong;Jianting Hu;Mei Li;Q. Guan;Jiajun Zhao
西洛他唑和过氧化物酶体增殖物激活受体（PPARs）配体已被有效用于缓解糖尿病并发症，但糖尿病患者和接受西洛他唑治疗的患者不同组织中PPARs的常见和组织特异性表达模式尚未见报道。在此，我们旨在评估糖尿病和西洛他唑对接受西洛他唑治疗 8 周的糖尿病大鼠的主动脉、肾皮质和视网膜中 PPARα 和 PPARgamma mRNA 表达的影响。在糖尿病大鼠的所有这些组织中，PPARα mRNA 表达均显示出一致的下调，并且这种效应可以通过西洛他唑治疗逆转。令人惊讶的是，糖尿病大鼠的肾皮质和视网膜中的 PPARgamma mRNA 表达减少，而主动脉中的表达增加，尽管西洛他唑仍然逆转了这些变化。有趣的是，西洛他唑（一种著名的磷酸二酯酶 3 抑制剂和 cAMP 升高剂）仅增加主动脉中的 cAMP 含量，但对糖尿病大鼠的肾皮质没有显着影响。总之，糖尿病中 PPAR 的 mRNA 表达具有组织特异性，并且可能受到西洛他唑的不同影响，可能是因为它对 cAMP 含量的组织特异性影响。
Cilostazol and ligands of peroxisome proliferator-activated receptors (PPARs) have been effectively used to alleviate diabetic complications, but the common and tissue-specific expression patterns of PPARs in different tissues in diabetic patients and those treated with cilostazol have not been reported. Here, we aimed to assess the effects of diabetes and cilostazol on mRNA expression of PPARalpha and PPARgamma in the aorta, renal cortex, and retina of diabetic rats treated with cilostazol for 8 weeks. PPARalpha mRNA expression showed uniform downregulation in all these tissues in diabetic rats, and this effect was reversed by cilostazol treatment. Surprisingly, PPARgamma mRNA expression was reduced in the renal cortex and retina, yet increased in the aorta of diabetic rats, although cilostazol still reversed these changes. Interestingly, cilostazol, a well-known phosphodiesterase 3 inhibitor and cAMP elevator, augmented cAMP content only in the aorta, but showed no significant effects in the renal cortex of diabetic rats. In conclusion, mRNA expression of PPARs is tissue-specific in diabetes and may be differently affected by cilostazol, possibly because of its tissue-specific effects on cAMP content.