Induction of innervation by encapsulated adipocytes with engineered vitamin A metabolism.
Induction of innervation by encapsulated adipocytes with engineered vitamin A metabolism.
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DOI：
10.1016/j.trsl.2017.10.005
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Ziouzenkova O
中科院分区：
文献类型：
--
作者：
Shen Q;Yasmeen R;Marbourg J;Xu L;Yu L;Fadda P;Flechtner A;Lee LJ;Popovich PG;Ziouzenkova O
神经支配是组织功能和生存的基本基础。在外周组织中，退行性疾病造成神经毒性代谢环境，导致神经退化或无法维持受伤/患病组织的再生生长和再神经支配。包裹产生神经营养因子的细胞可以促进轴突生长和神经元存活；然而，体内持续的神经支配需要促进轴突生长的因子和在特定组织背景下释放的引导途径的组合。利用新的包埋技术和基因工具，我们在脂肪细胞中操纵了维甲酸生成酶乙醛脱氢酶1a1(Aldh1a1)，该酶能够通过交感神经元促进白色脂肪组织的生长和神经支配。ALDH1A1−/−脂肪细胞分泌调节轴突导向的分子，并在体外和体内显著刺激轴突生长。基于对天然和人工合成的RAR激动剂和拮抗剂、基因芯片和纳米串阵列的研究，我们得出结论：eph in A5/eph in A4是受Aldh1a1调控的下游通路。海藻酸多L赖氨酸微囊包裹Aldh1a1−/−脂肪细胞可诱导肥胖野生型小鼠脂肪组织的功能性神经支配。我们认为包裹的Aldh1a1−/−脂肪细胞可以为受损组织的神经再支配提供一种治疗方案。
Innervation is a fundamental basis for function and survival of tissues. In the peripheral tissues, degenerative diseases create a neurotoxic metabolic milieu that either causes neurodegeneration or fails to sustain regenerative growth and re-innervation of injured/diseased tissues. Encapsulation of cells producing neurotrophic factors can augment axon growth and neuron survival; however, sustained innervation in vivo requires a combination of factors promoting axon growth and guidance pathway that are released in a tissue-specific context. Using novel encapsulation techniques and genetic tools, we manipulated retinoic acid-generating enzyme aldehyde dehydrogenase 1a1 (Aldh1a1) in adipocytes that is capable of promoting growth and innervation of white adipose tissue (WAT) by sympathetic neurons. Aldh1a1−/− adipocytes secrete molecules that regulate axon-guidance and markedly stimulate neurite outgrowth in vitro and in vivo. Based on studies with natural and synthetic RAR agonists and antagonists, gene microarray and nanostring arrays, we concluded that ephrin A5/ephrin A4 is a downstream pathway regulated by Aldh1a1. Encapsulation of Aldh1a1−/− adipocytes into alginate poly-L-lysine microcapsules induced functional innervation of adipose tissue in obese wild-type mice. We propose that encapsulated Aldh1a1−/− adipocytes could provide a therapeutic solution for the reinnervation of damaged tissues.
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视网膜甲醛脱氢酶1调节白色脂肪组织中的热程序。
影响因子：
82.9
作者：
通讯作者：
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影响因子：
7.1
作者：
Edwards, Lesley A.;Bugaresti, Joanne M.;Buchholz, Andrea C.
通讯作者：
Buchholz, Andrea C.
DOI：
10.1038/ijosup.2015.9
发表时间：
2015-08-01
期刊：
International journal of obesity supplements
影响因子：
--
作者：
Bartness, T J;Ryu, V
通讯作者：
Ryu, V
影响因子：
4.2
作者：
Inskip, Jessica;Plunet, Ward;Krassioukov, Andrei
通讯作者：
Krassioukov, Andrei
DOI：
10.1523/jneurosci.3992-08.2009
发表时间：
2009-03-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gensel JC;Nakamura S;Guan Z;van Rooijen N;Ankeny DP;Popovich PG
通讯作者：
Popovich PG