Renal gene expression in embryonic and newborn diabetic mice.
Renal gene expression in embryonic and newborn diabetic mice.
复制标题
胚胎和新生糖尿病小鼠的肾脏基因表达。
DOI：
10.1159/000049908
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Kanwar,YashpalS
中科院分区：
文献类型：
--
作者：
Wallner,ElisabethI;Wada,Jun;Lin,Sun;Pan,Xiaomin;Reddy,JanaradanK;Chugh,SumantS;Kanwar,YashpalS
几个在糖尿病肾脏中上调的新基因已经被发现。最近，转化生长因子β驱动的分泌性蛋白，即结缔组织生长因子和Gremlin(骨形态发生蛋白2)被发现，它们的表达与成人糖尿病肾病的组织变化有关。然而，很少有文献报道描述糖尿病状态下胚胎和新生儿生命过程中的基因表达。众所周知，在器官培养系统中，暴露于葡萄糖或其同分异构体，即甘露糖，会导致胚胎后肾的显著畸形发生。这些变化与ATP耗竭和显著的细胞凋亡有关，提示氧化应激在诱导胚胎后肾畸形发生中起作用。针对葡萄糖引起的胎儿后肾的改变，在妊娠期间给予链脲佐菌素诱导糖尿病状态，并对新生小鼠肾脏进行抑制消减杂交-聚合酶链式反应。另外，建立新生糖尿病小鼠的糖尿病模型，1周后取肾脏进行基因表达差异分析。发现了4个新的上调表达的基因。它们包括：(1)线粒体膜内转位酶44，它参与依赖于ATP的前蛋白从胞浆输入到线粒体基质中；(2)肾脏特异的醛酮还原酶，它利用NADPH和NADH作为辅助因子还原芳香醛和醛已糖；(3)Rap1b是一种RAS相关的小GTP结合蛋白，其功能类似于GTP酶，并且在GTP结合(活跃)和GDP结合(非活跃)状态之间循环与构象变化相关；以及(4)泛素多肽和核糖体蛋白L40(Uba 52或ubiquitin/60)的融合蛋白，它密切参与泛素依赖的蛋白酶体途径，该途径与各种应激条件下蛋白质的加速降解有关，如在癌症和糖尿病患者中看到的情况。
Several novel genes that are upregulated in diabetic kidneys have been identified. Recently, transforming growth factor beta driven secreted proteins, ie, connective tissue growth factor and gremlin (bone morphogenetic protein 2), have been identified, and their expression has been correlated with the tissue changes seen in diabetic nephropathy in the adult population. However, there are very few studies reported in the literature that describe the gene expression in the diabetic state during embryonic and neonatal life. It is well known that exposure to glucose or its epimer, ie, mannose, induces marked dysmorphogenesis of the embryonic metanephros in an organ culture system. These changes are associated with ATP depletion and marked apoptosis, suggesting an oxidant stress in the induction of dysmorphogenesis of the embryonic metanephros. In view of the glucose-induced changes in the fetal metanephros, a diabetic state was induced by the administration of streptozotocin during pregnancy, and newborn mouse kidneys were processed for suppression subtractive hybridization-PCR. In addition, a diabetic state was induced in newborn diabetic mice, and after 1 week their kidneys were harvested and subjected to representational difference analysais of cDNA. Four novel genes with upregulated mRNA expression were identified. They included:(1) a translocase inner mitochondrial membrane 44 that is involved in the ATP-dependent import of preproteins from the cytosol into the mitochondrial matrix;(2) a kidney-specific aldo-keto reductase that utilizes NADPH and NADH as cofactors in the reduction of aromatic aldehydes and aldohexoses;(3) Rap1b, a Ras-related small GTP-binding protein that behaves as a GTPase and cycles between GTP-bound (active) and GDP-bound (inactive) states associated with conformational change, and (4) a fusion protein of ubiquitin polypeptide and ribosomal protein L40 (UbA 52 or ubiquitin/60) that is intimately involved in the ubiquitin-dependent proteasome pathway related to the accelerated degradation of proteins under various stress conditions, such as those seen in patients with cancer and diabetes mellitus.