Cheng Yuan, Yulu Ye, Yinjie Zhou, Lu Xu, Tingzhuang Yi, Lihua Ni
{"title":"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。","authors":"Cheng Yuan, Yulu Ye, Yinjie Zhou, Lu Xu, Tingzhuang Yi, Lihua Ni","doi":"10.1159/000548252","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"1-23"},"PeriodicalIF":2.1000,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of GALNT14 as a Key Regulator of Ferroptosis in Cisplatin-Induced Acute Kidney Injury: A Potential Target for Kidney Injury Treatment.\",\"authors\":\"Cheng Yuan, Yulu Ye, Yinjie Zhou, Lu Xu, Tingzhuang Yi, Lihua Ni\",\"doi\":\"10.1159/000548252\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":17813,\"journal\":{\"name\":\"Kidney & blood pressure research\",\"volume\":\" \",\"pages\":\"1-23\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-09-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kidney & blood pressure research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000548252\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney & blood pressure research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000548252","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
Identification of GALNT14 as a Key Regulator of Ferroptosis in Cisplatin-Induced Acute Kidney Injury: A Potential Target for Kidney Injury Treatment.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
