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肾组织中 ALOX12 的升高可预测糖尿病肾病的进展。

Elevated ALOX12 in renal tissue predicts progression in diabetic kidney disease.

机构信息

Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Center for Scientific Research of Anhui Medical University, Hefei, China.

出版信息

Ren Fail. 2024 Dec;46(1):2313182. doi: 10.1080/0886022X.2024.2313182. Epub 2024 Feb 12.

Abstract

Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease and one of the significant complications of diabetes. This study aims to identify the main differentially expressed genes in DKD from transcriptome sequencing results and analyze their diagnostic value. The present study sequenced db/m mouse and db/db mouse to determine the ALOX12 genetic changes related to DKD. After preliminary validation, ALOX12 levels were significantly elevated in the blood of DKD patients, but not during disease progression. Moreover, urine ALOX12 was increased only in macroalbuminuria patients. Therefore, to visualize the diagnostic efficacy of ALOX12 on the onset and progression of renal injury in DKD, we collected kidney tissue from patients for immunohistochemical staining. ALOX12 was increased in the kidneys of patients with DKD and was more elevated in macroalbuminuria patients. Clinical chemical and pathological data analysis indicated a correlation between ALOX12 protein expression and renal tubule injury. Further immunofluorescence double staining showed that ALOX12 was expressed in both proximal tubules and distal tubules. Finally, the diagnostic value of the identified gene in the progression of DKD was assessed using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value for ALOX12 in the diagnosis of DKD entering the macroalbuminuria stage was 0.736, suggesting that ALOX12 has good diagnostic efficacy. During the development of DKD, the expression levels of ALOX12 in renal tubules were significantly increased and can be used as one of the predictors of the progression to macroalbuminuria in patients with DKD.

摘要

糖尿病肾病(DKD)是终末期肾病的主要病因之一,也是糖尿病的重要并发症之一。本研究旨在从转录组测序结果中鉴定出 DKD 中的主要差异表达基因,并分析其诊断价值。本研究对 db/m 小鼠和 db/db 小鼠进行了测序,以确定与 DKD 相关的 ALOX12 遗传变化。经过初步验证,DKD 患者的血液中 ALOX12 水平显著升高,但在疾病进展过程中没有升高。此外,只有在大量白蛋白尿患者中尿液 ALOX12 增加。因此,为了可视化 ALOX12 在 DKD 肾损伤发生和进展中的诊断功效,我们从患者中收集了肾组织进行免疫组织化学染色。在 DKD 患者的肾脏中,ALOX12 增加,在大量白蛋白尿患者中增加更为明显。临床化学和病理数据分析表明,ALOX12 蛋白表达与肾小管损伤之间存在相关性。进一步的免疫荧光双重染色显示 ALOX12 在近端肾小管和远端肾小管中均有表达。最后,使用受试者工作特征(ROC)曲线分析评估了鉴定基因在 DKD 进展中的诊断价值。ALOX12 诊断 DKD 进入大量白蛋白尿阶段的曲线下面积(AUC)值为 0.736,表明 ALOX12 具有良好的诊断功效。在 DKD 的发展过程中,肾小管中 ALOX12 的表达水平显著增加,可作为 DKD 患者进展为大量白蛋白尿的预测指标之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de96/10863531/05b638f7d745/IRNF_A_2313182_F0001_C.jpg

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