Identification of GALNT14 as a Key Regulator of Ferroptosis in Cisplatin-Induced Acute Kidney Injury: A Potential Target for Kidney Injury Treatment.

IF 2.1 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Kidney & blood pressure research Pub Date : 2025-09-04 DOI:10.1159/000548252

Cheng Yuan, Yulu Ye, Yinjie Zhou, Lu Xu, Tingzhuang Yi, Lihua Ni

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引用次数: 0

Abstract

Objective: Cisplatin-induced acute kidney injury (Cis-AKI) is a significant cause of renal damage, characterized by tubular injury, ferroptosis, and oxidative stress. While therapeutic options for Cis-AKI remain limited, identifying novel targets to prevent kidney injury is critical. This study focuses on GALNT14, a gene associated with ferroptosis, and its potential role in mitigating Cis-AKI.

Methods: Differentially expressed genes (DEGs) between saline and cisplatin group were analyzed using Limma package. The weighted correlation network analysis (WGCNA) was performed to identify the co-expressed modules and hub genes associated with Cis-AKI. The hub genes were then put into String database to create a network of protein-protein interactions (PPI). The ferroptosis-related genes (FRGs) were obtained from the FerrDb database, which screening for ferroptosis associated with CiS-AKI. The role of GALNT14 was examined in vitro using HK-2 renal tubular cells and in vivo in a Cis-AKI murine model.

Results: Totally, 1201 DEGs in intravenous (iv) administration group were retrieved. The 806 genes were obtained from intersection WGCNA and DEGs. Ultimately, we identified 4 genes (ALOX5, CD44, GALNT14 and ASNS) that may play important roles in the regulation of ferroptosis in CiS-AKI. Among them, the mRNA expression level of GALNT14 showed the most significant difference between Cis-AKI and the control group. In vitro, GALNT14 overexpression in HK-2 cells reduced renal injury and ferroptosis markers, including KIM1, NGAL, and FSP1, while increasing GPX4 expression. Conversely, silencing GALNT14 exacerbated Cis-AKI-induced injury. In vivo, GALNT14 overexpression in Cis-AKI mice attenuated kidney injury, reduced ferroptosis markers, and reversed pathological alterations such as tubular dilatation and loss of brush border.

Conclusion: GALNT14 inhibits Cis-AKI by regulating tubular ferroptosis, demonstrating its potential as a therapeutic target for kidney injury. Our findings suggest that GALNT14 could be an effective strategy for preventing Cis-AKI and improving renal function in kidney injury-related diseases.

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GALNT14在顺铂诱导的急性肾损伤中作为铁凋亡的关键调节因子的鉴定：肾损伤治疗的潜在靶点。

目的：顺铂诱导的急性肾损伤（Cis-AKI）是肾损害的重要原因，以肾小管损伤、铁下垂和氧化应激为特征。虽然Cis-AKI的治疗选择仍然有限，但确定新的靶点来预防肾损伤至关重要。这项研究的重点是GALNT14，一个与铁下垂相关的基因，及其在减轻顺式aki中的潜在作用。方法：采用Limma包检测生理盐水组与顺铂组的差异表达基因（DEGs）。采用加权相关网络分析（WGCNA）鉴定与Cis-AKI相关的共表达模块和枢纽基因。然后将中心基因放入String数据库以创建蛋白质-蛋白质相互作用（PPI）网络。从ferdb数据库中获得铁下垂相关基因（FRGs），用于筛选CiS-AKI相关的铁下垂。在体外用HK-2肾小管细胞和体内用Cis-AKI小鼠模型检测GALNT14的作用。结果：静脉（iv）给药组共检索到deg 1201个。806个基因来自WGCNA和deg的交集。最终，我们确定了4个基因（ALOX5、CD44、GALNT14和ASNS）可能在CiS-AKI中铁下垂的调控中发挥重要作用。其中，GALNT14 mRNA表达水平在Cis-AKI与对照组之间差异最为显著。在体外，在HK-2细胞中，GALNT14过表达减少了肾损伤和铁凋亡标志物，包括KIM1、NGAL和FSP1，同时增加了GPX4的表达。相反，沉默GALNT14会加重cis - aki诱导的损伤。在体内，GALNT14在Cis-AKI小鼠中的过表达减轻了肾损伤，降低了铁下垂标志物，并逆转了肾小管扩张和刷状边界丧失等病理改变。结论：GALNT14通过调节肾小管铁下垂抑制Cis-AKI，显示其作为肾损伤治疗靶点的潜力。我们的研究结果表明GALNT14可能是预防顺式aki和改善肾损伤相关疾病肾功能的有效策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Kidney & blood pressure research 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.