Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress.
Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress.
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胎球蛋白-A是HIF的靶标，在低氧应激期间保护组织的完整性。
DOI：
10.1038/s41467-020-20832-7
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发表时间：
2021-01-22
影响因子：
16.6
通讯作者：
Huynh-Do U
中科院分区：
文献类型：
--
作者：
Rudloff S;Janot M;Rodriguez S;Dessalle K;Jahnen-Dechent W;Huynh-Do U
宫内生长受限（IUGR）与出生时肾脏大小减小、肾功能加速下降以及成人慢性肾脏和心血管疾病的风险增加有关。胎儿规划成人疾病的确切机制仍然难以捉摸，需要广泛的研究。建立小鼠缺氧诱导IUGR模型，以肾脏为读数，在mRNA、蛋白和细胞水平上对胎儿的适应及其长期功能后果进行表征。在这里，我们确定了胎儿蛋白a是一个进化保守的HIF靶基因，并通过胎儿蛋白a KO动物和成年缺血再灌注损伤模型进一步研究其作用。除了作为全身性钙化抑制剂的作用外，胎蛋白a还作为一种多方面的保护因子，局部抵消钙化，调节巨噬细胞极化，减轻炎症和纤维化，从而保护肾功能。我们的研究为减轻矿物质应激引起的炎症和损伤的治疗方法铺平了道路，主要适用于所有软组织。宫内生长受限与成人慢性疾病风险增加有关。在这里，作者确定了胎儿蛋白a作为HIF靶基因，并描述了其在肾脏中的保护作用，抵消疾病机制，如钙化、巨噬细胞极化和纤维化。
Intrauterine growth restriction (IUGR) is associated with reduced kidney size at birth, accelerated renal function decline, and increased risk for chronic kidney and cardiovascular diseases in adults. Precise mechanisms underlying fetal programming of adult diseases remain largely elusive and warrant extensive investigation. Setting up a mouse model of hypoxia-induced IUGR, fetal adaptations at mRNA, protein and cellular levels, and their long-term functional consequences are characterized, using the kidney as a readout. Here, we identify fetuin-A as an evolutionary conserved HIF target gene, and further investigate its role using fetuin-A KO animals and an adult model of ischemia-reperfusion injury. Beyond its role as systemic calcification inhibitor, fetuin-A emerges as a multifaceted protective factor that locally counteracts calcification, modulates macrophage polarization, and attenuates inflammation and fibrosis, thus preserving kidney function. Our study paves the way to therapeutic approaches mitigating mineral stress-induced inflammation and damage, principally applicable to all soft tissues. Intrauterine growth restriction is associated with increased risk for chronic diseases in adults. Here the authors identify fetuin-A as a HIF target gene and describe its protective role in the kidney, counteracting disease mechanisms such as calcification, macrophage polarization, and fibrosis.
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DOI：
10.1096/fj.201500057
发表时间：
2016-05
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Allison BJ;Kaandorp JJ;Kane AD;Camm EJ;Lusby C;Cross CM;Nevin-Dolan R;Thakor AS;Derks JB;Tarry-Adkins JL;Ozanne SE;Giussani DA
通讯作者：
Giussani DA
DOI：
10.1073/pnas.1208916109
发表时间：
2012-08-28
影响因子：
11.1
作者：
Boonrungsiman, Suwimon;Gentleman, Eileen;Stevens, Molly M.
通讯作者：
Stevens, Molly M.
影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
影响因子：
4.8
作者：
Heiss, A;DuChesne, A;Jahnen-Dechent, W
通讯作者：
Jahnen-Dechent, W
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y