Serum Amyloid A3 Promoter-Driven Luciferase Activity Enables Visualization of Diabetic Kidney Disease.
Serum Amyloid A3 Promoter-Driven Luciferase Activity Enables Visualization of Diabetic Kidney Disease.
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DOI：
10.3390/ijms23020899
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发表时间：
2022-01-14
影响因子：
5.6
通讯作者：
Yanaka N
中科院分区：
文献类型：
--
作者：
Saliu TP;Yazawa N;Hashimoto K;Miyata K;Kudo A;Horii M;Kamesawa M;Kumrungsee T;Yanaka N
糖尿病肾病(DN)的早期检测对于药物和功能食品的开发是必要的。这项研究的目的是识别在糖尿病肾病进展的早期阶段显著上调的基因，并开发一种新的模型，利用活体成像技术非侵入性地监测活体动物的疾病进展。链脲佐菌素(STZ)作为糖尿病肾病模型已被广泛应用，但其对肾脏也表现出直接的细胞毒性。由于区分糖尿病肾病和STZ肾病是很重要的，在这项研究中，我们比较了糖尿病环境和两种类型的STZ模型引起的肾脏反应：多次注射低剂量的STZ配合高脂饮食和两次中等剂量的STZ注射以诱导糖尿病肾病。我们发现221个基因在两种模型的糖尿病肾病发展过程中表达显著改变，并确定血清淀粉样蛋白A3(Saa3)为候选基因。接下来，我们将Saa3启动子驱动的荧光素酶报告基因(Saa3启动子LUC小鼠)应用于这两个STZ模型，并进行体内生物发光成像以监测肾脏病理的进展。在这项研究中，为了进一步排除体内生物发光信号与STZ处理的肾脏细胞毒性有关的可能性，我们将胰岛素注射到Saa3启动子LUC小鼠中，结果表明胰岛素处理可以下调肾脏的炎症反应，体内生物发光成像的信号强度降低。这些结果有力地表明，Saa3启动子的活性是一种有效的非侵入性指标，可用于监测糖尿病肾病的进展，并探索治疗药物和功能食品。
The early detection of diabetic nephropathy (DN) in mice is necessary for the development of drugs and functional foods. The purpose of this study was to identify genes that are significantly upregulated in the early stage of DN progression and develop a novel model to non-invasively monitor disease progression within living animals using in vivo imaging technology. Streptozotocin (STZ) treatment has been widely used as a DN model; however, it also exhibits direct cytotoxicity to the kidneys. As it is important to distinguish between DN-related and STZ-induced nephropathy, in this study, we compared renal responses induced by the diabetic milieu with two types of STZ models: multiple low-dose STZ injections with a high-fat diet and two moderate-dose STZ injections to induce DN. We found 221 genes whose expression was significantly altered during DN development in both models and identified serum amyloid A3 (Saa3) as a candidate gene. Next, we applied the Saa3 promoter-driven luciferase reporter (Saa3-promoter luc mice) to these two STZ models and performed in vivo bioluminescent imaging to monitor the progression of renal pathology. In this study, to further exclude the possibility that the in vivo bioluminescence signal is related to renal cytotoxicity by STZ treatment, we injected insulin into Saa3-promoter luc mice and showed that insulin treatment could downregulate renal inflammatory responses with a decreased signal intensity of in vivo bioluminescence imaging. These results strongly suggest that Saa3 promoter activity is a potent non-invasive indicator that can be used to monitor DN progression and explore therapeutic agents and functional foods.
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影响因子：
4.6
作者：
Sanada Y;Yamamoto T;Satake R;Yamashita A;Kanai S;Kato N;van de Loo FA;Nishimura F;Scherer PE;Yanaka N
通讯作者：
Yanaka N
影响因子：
6.1
作者：
Meek, Rick L.;LeBoeuf, Renee C.;Tuttle, Katherine R.
通讯作者：
Tuttle, Katherine R.
影响因子：
82.9
作者：
Niewczas, Monika A.;Pavkov, Meda E.;Krolewski, Andrzej S.
通讯作者：
Krolewski, Andrzej S.
影响因子：
7.3
作者：
Sorić Hosman I;Kos I;Lamot L
通讯作者：
Lamot L
影响因子：
19.6
作者：
Chow, FY;Nikolic-Paterson, DJ;Tesch, GH
通讯作者：
Tesch, GH