[1]任慧雯,王秋月.Epac-Rap1与糖尿病肾病[J].国际内分泌代谢杂志,2015,(03):170-172.[doi:10.3760/cma.j.issn.1673-4157.2015.03.007]
　Ren Huiwen,Wang Qiuyue..Epac-Rap1 and diabetic nephropathy[J].International Journal of Endocrinology and Metabolism,2015,(03):170-172.[doi:10.3760/cma.j.issn.1673-4157.2015.03.007]
点击复制

Epac-Rap1与糖尿病肾病()
分享到：

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
期数:
2015年03
页码:
170-172
栏目:
肾脏疾病专栏
出版日期:
2015-05-20

文章信息/Info

Title:
Epac-Rap1 and diabetic nephropathy
作者:
任慧雯; 王秋月
110001　沈阳，中国医科大学附属第一医院内分泌科 　　
Author(s):
Ren Huiwen; Wang Qiuyue.
Department of Endocrinology，The First Affiliated Hospital，Chinese Medical University，Shenyang 110001，China Corresponding author：Wang Qiuyue，Email：wqycmu@163.com
关键词:
糖尿病肾病; Epac; Rap1
Keywords:
Diabetic nephropathy; Epac; Rap1
DOI:
10.3760/cma.j.issn.1673-4157.2015.03.007
摘要:
Epac-Rap1通路是蛋白激酶A经典通路以外cAMP重要的效应通路，它在肾脏中的广泛表达，能够增强肾脏血管内皮细胞的屏障功能，影响细胞的连接、黏附和迁移，对肾脏的生理活动起到不可或缺的作用。近年研究表明，Epac-Rap1信号通路激活下游信号级联系统，通过促进细胞肥大、介导肾间质纤维化、上调炎性反应细胞因子的表达，促进糖尿病肾病的病理生理改变。相关研究为理解糖尿病肾病状态下Epac-Rap1通路的作用拓宽了视野，有助于发现分子水平治疗糖尿病肾病的新靶点。
Abstract:
Epac-Rap1 pathway is a vital signal pathway of cAMP apart from classic protein kinase A pathway，and its widely expression in kidney enhances the barrier function of renal vascular endothelial cells and affects cell connection，adhesion and migration，which plays a vital role in the physiological activity of the kidney. Recent studies have found that Epac-Rap1 signaling pathway，which activates downstream signaling cascade systems，plays a significant role in the pathophysiology of diabetic nephropathy by promoting cell hypertrophy，mediating renal interstitial fibrosis and up-regulating the expression of inflammatory cytokines. Related studies have broadened our understanding of Epac-Rap1 pathway and its function in diabetic nephropathy，which is helpful to find out a new target in the molecular level for the treatment of diabetic nephropathy.

参考文献/References:

[1]　Bos JL.Epac：a new cAMP target and new avenues in cAMP research [J].Nat Rev Mol Cell Biol，2003，4（9）：733-738. 　
[2]　Kawasaki H，Springett GM，Mochizuki N，et al.A family of cAMP-binding proteins that directly activate Rap1[J].Science，1998，282（5397）：2275-2279. 　
[3]　Rehmann H，Das J，Knipscheer P，et al.Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state [J]. Nature，2006，439（7076）：625-628. 　
[4]　Ji Z，Mei FC，Cheng X. Epac，not PKA catalytic subunit，is required for 3T3-L1 preadipocyte differentiation [J].Front Biosci （Elite Ed），2010，2：392-398. 　
[5]　Guvakova MA，Lee WS，Furstenau DK，et al.The small GTPase Rap1 promotes cell movement rather than stabilizes adhesion in epithelial cells responding to insulin-like growth factorⅠ[J].Biochem J， 2014，463（2）：257-270. 　
[6]　Wilson CW，Parker LH，Hall CJ，et al.Rasip1 regulates vertebrate vascular endothelial junction stability through Epac1-Rap1 signaling [J].Blood，2013，122（22）：3678-3690. 　
[7]　Cyphert HA，Alonge KM，Ippagunta SM，et al.Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent posttranscriptional mechanism [J].PLoS One，2014，9（4）：e94996. 　
[8]　Ponsioen B，Gloerich M，Ritsma L，et al.Direct spatial control of Epac1 by cyclic AMP [J].Mol Cell Biol，2009，29（10）：2521-2531. 　
[9]　Spindler V，Peter D，Harms GS，et al.Ultrastructural analysis reveals cAMP-dependent enhancement of microvascular endothe-lial barrier functions via Rac1-mediated reorganization of inter-cellular junctions [J].Am J Pathol，2011，178（5）：2424-2436.
[10]　Aslam M，Schluter KD，Rohrbach S，et al.Hypoxia-reoxygenation-induced endothelial barrier failure：role of RhoA，Rac1 and myosin light chain kinase [J].J Physiol，2013，591（Pt 2）：461-473.
[11]　Sehrawat S，Ernandez T，Cullere X，et al.AKAP9 regulation of microtubule dynamics promotes Epac1-induced endothelial barrier properties [J].Blood，2011，117（2）：708-718.
[12]　Rufanova VA，Alexanian A，Ostendorf T，et al.Endothelin signaling via guanine exchange factor C3G in renal glomerular mesangial cells [J].Can J Physiol Pharmacol，2010，88（8）：808-816.
[13]　Rufanova VA，Lianos E，Alexanian A，et al.C3G overexpression in glomerular epithelial cells during anti-GBM-induced glomeru-lonephritis [J].Kidney Int，2009，75（1）：31-40.
[14]　Kanwar YS，Sun L，Xie P，et al.A glimpse of various pathogenetic mechanisms of diabetic nephropathy[J].Annu Rev Pathol，2011，6：395-423.
[15]　Métrich M，Lucas A，Gastineau M，et al.Epac mediates beta-adrenergic receptor-induced cardiomyocyte hypertrophy[J].Circ Res，2008，102（8）：959-965.
[16]　Sun L，Kondeti VK，Xie P，et al.Epac1-mediated， high glucose-induced renal proximal tubular cells hypertrophy via the Akt/p21 pathway[J].Am J Pathol，2011，179（4）：1706-1718.
[17]　Miller CL，Cai Y，Oikawa M，et al.Cyclic nucleotide phosphodi-esterase 1A：a key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart[J].Basic Res Cardiol，2011，106（6）：1023-1039.
[18]　Yano N，Suzuki D，Endoh M，et al.A novel phosphoinositide 3-kinase-dependent pathway for angiotensin Ⅱ/AT-1 receptor-mediated induction of collagen synthesis in MES-13 mesangial cells[J].J Biol Chem，2007，282（26）：18819-18830.
[19]　Lin S，Chugh S，Pan X，et al.Identification of up-regulated Ras-like GTPase，Rap1b，by suppression subtractive hybridization[J].Kidney Int，2001，60（6）：2129-2141.
[20]　Lin S，Sahai A，Chugh SS，et al.High glucose stimulates synthesis of fibronectin via a novel protein kinase C，Rap1b，and B-Raf signaling pathway[J].J Biol Chem，2002，277（44）：41725-41735.
[21]　Xie P，Joladarashi D，Dudeja P，et al.Modulation of angiotensin Ⅱ-induced inflammatory cytokines by the Epac1-Rap1A-NHE3 pathway：implications in renal tubular pathobiology[J].Am J Physiol Renal Physiol，2014，306（11）：F1260-F1274.

相似文献/References:

[1].2007年糖尿病新进展学习班将举办[J].国际内分泌代谢杂志,2007,(04):226.
[2]李英,段惠军.Raf/MEK/ERK信号转导通路在糖尿病肾病发生发展中的作用[J].国际内分泌代谢杂志,2007,(04):264.
[3]张红 章向成 朱大龙.炎性反应与糖尿病肾病[J].国际内分泌代谢杂志,2015,(01):49.[doi:10.3760/cma.j.issn.1673-4157.2015.01.012]
　Zhang Hong*,Zhang Xiangcheng,Zhu Dalong..Role of inflammation in diabetic nephropathy[J].International Journal of Endocrinology and Metabolism,2015,(03):49.[doi:10.3760/cma.j.issn.1673-4157.2015.01.012]
[4]邵滢,王秋月.Mir-217/Sirt1通路与糖尿病肾病[J].国际内分泌代谢杂志,2015,(02):124.[doi:10.3760/cma.j.issn.1673-4157.2015.02.014]
　Shao Ying,Wang Qiuyue..Mir-217 / Sirt1 pathway and diabetic nephropathy[J].International Journal of Endocrinology and Metabolism,2015,(03):124.[doi:10.3760/cma.j.issn.1673-4157.2015.02.014]
[5]王洁,何媛,于珮.糖尿病肾病的相关危险因素分析[J].国际内分泌代谢杂志,2015,(03):153.[doi:10.3760/cma.j.issn.1673-4157.2015.03.003]
　Wang Jie*,He Yuan,Yu Pei..Risk factors of diabetic nephropathy[J].International Journal of Endocrinology and Metabolism,2015,(03):153.[doi:10.3760/cma.j.issn.1673-4157.2015.03.003]
[6]邵滢,王秋月.MiRNA-150与糖尿病肾病[J].国际内分泌代谢杂志,2015,(03):173.[doi:10.3760/cma.j.issn.1673-4157.2015.03.008]
　Shao Ying,Wang Qiuyue..MiRNA-150 and diabetic nephropathy[J].International Journal of Endocrinology and Metabolism,2015,(03):173.[doi:10.3760/cma.j.issn.1673-4157.2015.03.008]
[7]陈堃,刘超,陈国芳,等.糖尿病肾病诊断标志物研究进展[J].国际内分泌代谢杂志,2015,(03):176.[doi:10.3760/cma.j.issn.1673-4157.2015.03.009]
　Chen Kun,Liu Chao,Chen Guofang,et al.Urinary biomarkers for diabetic nephropathy[J].International Journal of Endocrinology and Metabolism,2015,(03):176.[doi:10.3760/cma.j.issn.1673-4157.2015.03.009]
[8]任慧雯,王秋月.Vasohibin-1与糖尿病肾病[J].国际内分泌代谢杂志,2015,(04):246.[doi:10.3760/cma.j.issn.1673-4157.2015.04.008]
　Ren Huiwen,Wang Qiuyue..Vasohibin-1 and diabetic nephropathy[J].International Journal of Endocrinology and Metabolism,2015,(03):246.[doi:10.3760/cma.j.issn.1673-4157.2015.04.008]
[9]安丽,王秋月.Visfatin与胰岛素抵抗及糖尿病肾病的发病机制[J].国际内分泌代谢杂志,2015,(04):248.[doi:10.3760/cma.j.issn.1673-4157.2015.04.009]
　An Li,Wang Qiuyue..Visfatin in the pathogenesis of insulin resistance and diabetic nephropathy[J].International Journal of Endocrinology and Metabolism,2015,(03):248.[doi:10.3760/cma.j.issn.1673-4157.2015.04.009]
[10]任惠珠,王珊珊,郑妙艳,等.肾小球基底膜中胶原的合成、降解与糖尿病肾病[J].国际内分泌代谢杂志,2015,(04):252.[doi:10.3760/cma.j.issn.1673-4157.2015.04.010]
　Ren Huizhu,Wang Shanshan,Zheng Miaoyan,et al.Synthesis and degradation of collagen in glomerular basement membrane and their associations with diabetic nephropathy[J].International Journal of Endocrinology and Metabolism,2015,(03):252.[doi:10.3760/cma.j.issn.1673-4157.2015.04.010]

备注/Memo

备注/Memo:
基金项目：辽宁省科技攻关计划项目（2011225017）；沈阳市科技攻关计划项目（F11-262-9-06） 通信作者：王秋月，Email：wqycmu@163.com
更新日期/Last Update: 2015-05-20