Tissue-specific effects of targeted mutation of Mir29b1 in rats.
Tissue-specific effects of targeted mutation of Mir29b1 in rats.
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DOI：
10.1016/j.ebiom.2018.08.016
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发表时间：
2018-09
期刊：
影响因子：
11.1
通讯作者：
Liang M
中科院分区：
文献类型：
--
作者：
Xue H;Zhang G;Geurts AM;Usa K;Jensen DM;Liu Y;Widlansky ME;Liang M
miR-29 是细胞外基质基因的主要调节因子，但关于其抗纤维化作用的数据相互矛盾。 miR-29 通过靶向 Lypla1 来改善小动脉中一氧化氮 (NO) 的产生。在 Dahl 盐敏感大鼠模型中，Mir29b1 靶向突变会加剧高血压。我们研究了 Mir29b1 突变对组织纤维化和 NO 水平的影响，重点关注肾脏区域。 Mir29b1针对突变大鼠对SS-Chr13BN大鼠的遗传背景进行了研究。进行了马森三色染色、分子和生化测定、代谢笼研究以及人类基因组数据的生物信息学分析。突变大鼠中 miR-29b 和共转录 miR-29a 的丰度显着降低。在0.4% NaCl饮食的突变大鼠中，肾外髓质的组织纤维化显着增加，但肾皮质、心脏或肝脏的组织纤维化没有显着增加。在肾外髓质中，Lypla1 蛋白丰度显着较高，NO 水平较低，但在肾皮质中则不然。 4% NaCl饮食14天后，突变大鼠24小时尿量和尿钠排泄量显着降低，心脏组织纤维化程度更高。肾外髓质和心脏的 NO 水平较低，但肾皮质则不然。人类 miR-29 基因位于与血压相关的单核苷酸多态性附近。肾外髓质可能特别容易受到 miR-29 不足的损害，这可能导致 Mir29b1 突变大鼠患高血压。
miR-29 is a master regulator of extracellular matrix genes, but conflicting data on its anti-fibrotic effect have been reported. miR-29 improves nitric oxide (NO) production in arterioles by targeting Lypla1. Mir29b1 targeted mutation exacerbates hypertension in a model derived from the Dahl salt-sensitive rat. We examined the effect of Mir29b1 mutation on tissue fibrosis and NO levels with a focus on kidney regions. Mir29b1 targeted mutant rats on the genetic background of SS-Chr13BN rats were studied. Masson trichrome staining, molecular and biochemical assays, metabolic cage studies, and bioinformatic analysis of human genomic data were performed. The abundance of miR-29b and the co-transcribed miR-29a was substantially lower in mutant rats. Tissue fibrosis was significantly increased in the renal outer medulla, but not in the renal cortex, heart or liver in mutant rats on a 0.4% NaCl diet. Lypla1 protein abundance was significantly higher and NO levels lower in the renal outer medulla, but not in the renal cortex. After 14 days of a 4% NaCl diet, 24 h urine volume and urinary sodium excretion was significantly lower in mutant rats, and tissue fibrosis became higher in the heart. NO levels were lower in the renal outer medulla and heart, but not in the renal cortex. Human miR-29 genes are located in proximity with blood pressure-associated single nucleotide polymorphisms. The renal outer medulla might be particularly susceptible to the injurious effects of a miR-29 insufficiency, which might contribute to the development of hypertension in Mir29b1 mutant rats.
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影响因子：
3.7
作者：
Knabel MK;Ramachandran K;Karhadkar S;Hwang HW;Creamer TJ;Chivukula RR;Sheikh F;Clark KR;Torbenson M;Montgomery RA;Cameron AM;Mendell JT;Warren DS
通讯作者：
Warren DS
DOI：
10.1097/01.asn.0000060572.13794.58
发表时间：
2003-05-01
影响因子：
13.6
作者：
Garrett, MR;Dene, H;Rapp, JP
通讯作者：
Rapp, JP
DOI：
10.1152/ajprenal.00287.2012
发表时间：
2013-05-01
影响因子：
4.2
作者：
Fang, Yi;Yu, Xiaofang;Ding, Xiaoqiang
通讯作者：
Ding, Xiaoqiang
影响因子：
4.6
作者：
Liang, Mingyu;Lee, Norman H.;Cowley, Allen W., Jr.
通讯作者：
Cowley, Allen W., Jr.
影响因子：
4.6
作者：
Liu, Yong;Singh, Ravinder J.;Liang, Mingyu
通讯作者：
Liang, Mingyu