Identification of common and specific fibrosis-related genes in three common chronic kidney diseases.

IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Renal Failure Pub Date : 2024-12-01 Epub Date: 2024-01-04 DOI:10.1080/0886022X.2023.2295431
Zhangning Fu, Xiaodong Geng, Chao Liu, Wanjun Shen, Zheyi Dong, Guannan Sun, Guangyan Cai, Xiangmei Chen, Quan Hong
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Abstract

Background: Kidney fibrosis is the common final pathway of virtually all advanced forms of chronic kidney disease (CKD) including diabetic nephropathy (DN), IgA nephropathy (IgAN) and membranous nephropathy (MN), with complex mechanism. Comparative gene expression analysis among these types of CKD may shed light on its pathogenesis. Therefore, we conducted this study aiming at exploring the common and specific fibrosis-related genes involved in different types of CKD.

Methods: Kidney biopsy specimens from patients with different types of CKD and normal control subjects were analyzed using the NanoString nCounter® Human Fibrosis V2 Panel. Genes differentially expressed in all fibrotic DN, IgAN and MN tissues compared to the normal controls were regarded as the common fibrosis-related genes in CKD, whereas genes exclusively differentially expressed in fibrotic DN, IgAN or MN samples were considered to be the specific genes related to fibrosis in DN, IgAN and MN respectively. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of the selected genes.

Results: Protein tyrosine phosphatase receptor type C (PTPRC), intercellular cell adhesion molecule-1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), interleukin 10 receptor alpha (IL10RA) and CC chemokine receptor 2 (CCR2) were identified as the potential common genes for kidney fibrosis in different types of CKD, while peroxisome proliferator-activated receptor alpha (PPARA), lactate oxidase (LOX), secreted phosphoprotein 1 (SPP1) were identified as the specific fibrosis-associated genes for DN, IgAN and MN respectively. qRT-PCR demonstrated that the expression levels of these selected genes were consistent with the NanoString analysis.

Conclusions: There were both commonalities and differences in the mechanisms of fibrosis in different types of CKD, the commonalities might be used as the common therapeutic targets for kidney fibrosis in CKD, while the differences might be used as the diagnostic markers for DN, IgAN and MN respectively. Inflammation was highly relevant to the pathogenesis of fibrosis. This study provides further insight into the pathophysiology and treatment of fibrotic kidney disease.

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鉴定三种常见慢性肾病中常见和特异的纤维化相关基因。
背景:肾脏纤维化是糖尿病肾病(DN)、IgA 肾病(IgAN)和膜性肾病(MN)等几乎所有晚期慢性肾病(CKD)的共同终末途径,其发病机制十分复杂。对这些类型的 CKD 基因表达进行比较分析,可能会对其发病机制有所启发。因此,我们开展了这项研究,旨在探索不同类型 CKD 中常见和特异的纤维化相关基因:方法:使用 NanoString nCounter® Human Fibrosis V2 Panel 分析不同类型 CKD 患者和正常对照组的肾活检标本。与正常对照组相比,在所有纤维化的 DN、IgAN 和 MN 组织中差异表达的基因被视为 CKD 中常见的纤维化相关基因,而在纤维化的 DN、IgAN 或 MN 样品中完全差异表达的基因则分别被视为与 DN、IgAN 和 MN 纤维化相关的特异性基因。对所选基因的表达进行了定量实时 PCR(qRT-PCR)验证:结果:C型蛋白酪氨酸磷酸酶受体(PTPRC)、细胞间粘附分子-1(ICAM1)、血管细胞粘附分子-1(VCAM1)、白细胞介素10受体α(IL10RA)和CC趋化因子受体2(CCR2)被确定为不同类型CKD肾脏纤维化的潜在共同基因、而过氧化物酶体增殖激活受体α(PPARA)、乳酸氧化酶(LOX)和分泌型磷蛋白1(SPP1)则分别被确定为DN、IgAN和MN的特异性纤维化相关基因。qRT-PCR表明,这些选定基因的表达水平与NanoString分析结果一致:结论:不同类型的 CKD 肾脏纤维化机制既有共性也有差异,共性可作为 CKD 肾脏纤维化的共同治疗靶点,差异可分别作为 DN、IgAN 和 MN 的诊断标记。炎症与肾纤维化的发病机制高度相关。这项研究为纤维化肾病的病理生理学和治疗提供了进一步的见解。
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来源期刊
Renal Failure
Renal Failure 医学-泌尿学与肾脏学
CiteScore
3.90
自引率
13.30%
发文量
374
审稿时长
1 months
期刊介绍: Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.
期刊最新文献
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