Kidney Diseases最新文献_第9页

Long Noncoding RNA MEG3-205/Let-7a/MyD88 Axis Promotes Renal Inflammation and Fibrosis in Diabetic Nephropathy 长链非编码RNA MEG3-205/Let-7a/MyD88轴促进糖尿病肾病的肾脏炎症和纤维化

IF 3.7 4区医学

Kidney Diseases Pub Date : 2022-03-17 DOI: 10.1159/000523847

Q. Luo, X. Xia, Q. Luo, Y. Qiu, Lan Dong, Chen Zhao, F. Peng, Jing Yu, F. Huang, F. He

{"title":"Long Noncoding RNA MEG3-205/Let-7a/MyD88 Axis Promotes Renal Inflammation and Fibrosis in Diabetic Nephropathy","authors":"Q. Luo, X. Xia, Q. Luo, Y. Qiu, Lan Dong, Chen Zhao, F. Peng, Jing Yu, F. Huang, F. He","doi":"10.1159/000523847","DOIUrl":"https://doi.org/10.1159/000523847","url":null,"abstract":"Aim: The aim of this study was to investigate the role and mechanism of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3)-205 in renal inflammation and fibrosis in diabetic nephropathy (DN). Materials and Methods: lncRNA microarray profiling was used to examine differentially expressed lncRNAs of kidney tissues in db/db mice compared to db/m mice. Mouse mesangial cells (mMCs) were cultured in vitro with advanced glycation end products (AGEs) via transfection with lncRNA MEG3-205 siRNAs or plasmids. The role of lncRNA MEG3-205 in vivo was examined in db/db mice treated with long-acting lncRNA MEG3-205 siRNA. The interaction between lncRNA MEG3-205 and let-7a was investigated using luciferase assay and RNA immunoprecipitation assay. Results: lncRNA MEG3-205 was markedly upregulated in renal tissues of db/db mice, DN patients, and AGEs-treated mesangial cells. Overexpression of lncRNA MEG3-205 promoted the secretion of pro-inflammatory cytokines and synthesis of extracellular matrix proteins in mesangial cells. Both lncRNA MEG3-205 and myeloid differentiation primary-response protein 88 (MyD88) could bind to let-7a, and lncRNA MEG3-205 overexpression can significantly rescue the silencing effect of let-7a on MyD88 protein expression in mMCs. Mechanistically, we identified that lncRNA MEG3-205 could act as a competing endogenous RNA by binding with let-7a and thus regulate MyD88. Knockdown of lncRNA MEG3-205 alleviated albuminuria and attenuated renal inflammation and fibrosis in db/db mice. Conclusion: These findings indicated an important role of the lncRNA MEG3-205/let-7a/MyD88 axis in regulating renal inflammation and fibrosis in DN. Targeting lncRNA MEG3-205 might present a promising therapeutic strategy for DN.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"2014 1","pages":"231 - 245"},"PeriodicalIF":3.7,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86657456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Ischemic Preconditioning Alleviates Mouse Renal Ischemia/Reperfusion Injury by Enhancing Autophagy Activity of Proximal Tubular Cells 缺血预处理通过增强近端小管细胞自噬活性减轻小鼠肾缺血再灌注损伤

IF 3.7 4区医学

Kidney Diseases Pub Date : 2022-03-17 DOI: 10.1159/000521850

Shun Zhang, Weimin Xia, H. Duan, Xinyan Li, Subo Qian, Haibo Shen

{"title":"Ischemic Preconditioning Alleviates Mouse Renal Ischemia/Reperfusion Injury by Enhancing Autophagy Activity of Proximal Tubular Cells","authors":"Shun Zhang, Weimin Xia, H. Duan, Xinyan Li, Subo Qian, Haibo Shen","doi":"10.1159/000521850","DOIUrl":"https://doi.org/10.1159/000521850","url":null,"abstract":"Objectives: Ischemia/reperfusion injury (IRI) is one of the most vital pathogenesis leading to kidney injury but lacks effective prevention and treatment strategies. This study was conducted to investigate the influences of ischemic preconditioning (IPC) on the pathological process of mouse renal IRI (RIRI) and to figure out the role of autophagy of proximal tubular cells (PTCs) in this process. Methods: C57BL/6J mice were randomized to three groups, i.e., sham-operated group, ischemia/reperfusion (I/R) group, and IPC + I/R group. Meanwhile, 3-methyladenine, an autophagy inhibitor, was administered when further verification was needed. Histological and functional severity of kidney injury, the autophagy and apoptosis activity of PTCs, as well as the characterization of the immune cell infiltration landscape in kidney tissues were investigated. Furthermore, HK-2 cells and primary cultured PTC were cultured to set up the hypoxic preconditioning and hypoxia/reoxygenation model for in vitro simulation and verification, and a microarray dataset derived from the Gene Expression Omnibus database was analyzed to explore the transcriptome profiles after IPC. Results: IPC could significantly attenuate I/R-induced kidney injury functionally and histologically both in the acute and recovery phase of RIRI by enhancing the autophagy activity of PTCs. Cell autophagy could regulate the release of monocyte chemoattractant protein-1, and sequentially decrease macrophages infiltration in kidney tissues in the acute phase of RIRI, thus mediating the reno-protective effect. Conclusions: IPC could attenuate mouse RIRI-induced kidney injury. IPC-mediated activation of autophagy of PTCs plays a vital role in affording protection in RIRI-induced kidney injury.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"26 1","pages":"217 - 230"},"PeriodicalIF":3.7,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87959933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Metabolic Regulation of Fibroblast Activation and Proliferation during Organ Fibrosis 器官纤维化过程中成纤维细胞活化和增殖的代谢调控

IF 3.7 4区医学

Kidney Diseases Pub Date : 2022-03-01 DOI: 10.1159/000522417

Sudan Wang, Yan Liang, C. Dai

{"title":"Metabolic Regulation of Fibroblast Activation and Proliferation during Organ Fibrosis","authors":"Sudan Wang, Yan Liang, C. Dai","doi":"10.1159/000522417","DOIUrl":"https://doi.org/10.1159/000522417","url":null,"abstract":"Background: Activated fibroblasts are present in the injury response, tumorigenesis, fibrosis, and inflammation in a variety of tissues and myriad disease types. Summary: During normal tissue repair, quiescent fibroblasts transform into a proliferative and contractile phenotype termed myofibroblasts and are then lost as repair resolves to form a scar. When excessive levels are reached, activated fibroblasts proliferate and produce large amounts of extracellular matrix, which accumulates in the interstitial space of different organs. This accumulation leads to fibrotic dysfunction and multiple-organ dysfunction syndrome. To date, there are limited effective treatments for these conditions. Cellular metabolism is the cornerstone of all biological activities. Emerging evidence shows that metabolic alterations in fibroblasts are important for the activation process and illness progression. These discoveries, along with current clinical advances showing decreased lung fibrosis after targeting specific metabolic pathways, thus offer new possibilities for therapeutic interventions. The purpose of this review was to summarize the most recent knowledge of the major metabolic changes that occur during fibroblast transition from quiescent to activated states and the evidence linking alterations in fibroblast metabolism to the pathobiology of several common fibrotic diseases and tumor-related diseases. Key Messages: Metabolic disorders are associated with the progression of chronic kidney diseases. Interfering with fibroblast metabolism may be a promising therapeutic strategy for renal fibrosis and other fibrosis-related diseases.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"74 1","pages":"115 - 125"},"PeriodicalIF":3.7,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85248938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Front & Back Matter 正面和背面

IF 3.7 4区医学

Kidney Diseases Pub Date : 2022-03-01 DOI: 10.1159/000524215

Zhi-Hong Liu, J. Kopp

引用次数: 0

Loss of JNK-Associated Leucine Zipper Protein Promotes Peritoneal Dialysis-Related Peritoneal Fibrosis jnk相关亮氨酸拉链蛋白的缺失促进腹膜透析相关的腹膜纤维化

IF 3.7 4区医学

Kidney Diseases Pub Date : 2022-02-01 DOI: 10.1159/000521564

Maoqing Tian, Lu Zhang, Yujuan Wang, Meili Deng, Cancan Peng, W. Liang, G. Ding, Bo Shen, Huiming Wang

{"title":"Loss of JNK-Associated Leucine Zipper Protein Promotes Peritoneal Dialysis-Related Peritoneal Fibrosis","authors":"Maoqing Tian, Lu Zhang, Yujuan Wang, Meili Deng, Cancan Peng, W. Liang, G. Ding, Bo Shen, Huiming Wang","doi":"10.1159/000521564","DOIUrl":"https://doi.org/10.1159/000521564","url":null,"abstract":"Background: Peritoneal dialysis-related peritoneal fibrosis is the leading cause of peritoneal ultrafiltration failure. Multitude factors and pathological processes have been implicated in peritoneal fibrosis development and progression, whereas the intrinsic anti-fibrotic mechanism has rarely been explored. JNK-associated leucine zipper protein (JLP) has been recently found possessing powerful anti-fibrotic merits of overall antagonizing TGF-β-induced profibrotic effects. Objectives: We wondered whether JLP is expressed in the peritoneum, and if so, whether it exerts the anti-fibrotic effects similar to those in the kidney. Method: Here, we examined and confirmed JLP expression in peritoneum tissue of mice. Then, we established a peritoneal fibrosis model in Jlp wild-type and Jlp global deficient mice and observed the different effects of Jlp on peritoneal fibrosis progression. In vitro studies were performed on peritoneal mesothelial HMrSV5 cells with or without Jlp knockdown to investigate the underlying mechanism by which Jlp exerts anti-fibrotic effects. Results: We found that the expression of JLP decreased in a high-glucose peritoneal dialysis solution (HGPDS)-induced peritoneal fibrosis mouse model and in HGPDS-treated peritoneal mesothelial cell HMrSV5. JLP deletion exacerbated HGPDS-induced peritoneal fibrosis in peritoneal fibrosis mice, and knockdown of JLP resulted in an increased profibrotic response to HGPDS stimulation in HMrSV5 cells, which was associated with epithelial-to-mesenchymal transition, elevated autophagy, and apoptosis, as well as enhanced TGF-β1/Smad signaling activation. Conclusions: Our findings revealed a new anti-fibrotic factor of Jlp involved in peritoneal fibrosis induction and shed light on novel therapeutic targets in peritoneal ultrafiltration failure.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"40 1","pages":"168 - 179"},"PeriodicalIF":3.7,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90564396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Erythropoietin-Stimulating Agent Hyporesponsiveness in Patients Living with Chronic Kidney Disease 慢性肾病患者促红细胞生成素刺激剂低反应性

IF 3.7 4区医学

Kidney Diseases Pub Date : 2022-01-14 DOI: 10.1159/000521162

Henry H. L. Wu, R. Chinnadurai

{"title":"Erythropoietin-Stimulating Agent Hyporesponsiveness in Patients Living with Chronic Kidney Disease","authors":"Henry H. L. Wu, R. Chinnadurai","doi":"10.1159/000521162","DOIUrl":"https://doi.org/10.1159/000521162","url":null,"abstract":"Background: Erythropoietin-stimulating agent (ESA) hyporesponsiveness is commonly observed in patients with anemia secondary to chronic kidney disease (CKD). Because of its complexity, a global consensus on how we should define ESA hyporesponsiveness remains unavailable. The reported prevalence and demographic information on ESA hyporesponsiveness within the CKD population are variable with no consensus definition. Summary: ESA hyporesponsiveness is defined as having no increase in hemoglobin concentration from baseline after the first month of treatment on appropriate weight-based dosing. The important factors associated with ESA hyporesponsiveness include absolute or functional iron deficiency, inflammation, and uremia. Hepcidin has been demonstrated to play an important role in this process. Mineral bone disease secondary to CKD and non-iron malnutrition among other factors are also associated with ESA hyporesponsiveness. There is continued debate toward determining a gold-standard treatment pathway to manage ESA hyporesponsiveness. The development of hypoxia-inducing factor-stabilizers brings new insights and opportunities in the management of ESA hyporesponsiveness. Key Message: Management of ESA hyporesponsiveness involves a comprehensive multidisciplinary team approach to address its risk factors. The progression of basic and clinical research on identifying risk factors and management of ESA hyporesponsiveness brings greater hope on finding solutions to eventually tackling one of the most difficult problems in the topic of anemia in CKD.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"1 1","pages":"103 - 114"},"PeriodicalIF":3.7,"publicationDate":"2022-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78244529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Hydrogen: A Novel Treatment Strategy in Kidney Disease 氢:一种新的肾脏疾病治疗策略

IF 3.7 4区医学

Kidney Diseases Pub Date : 2022-01-12 DOI: 10.1159/000520981

Bo Wang, Zhuoshu Li, Longfei Mao, Mingyi Zhao, Bingchang Yang, Xi Tao, Yuxiang Li, Guangming Yin

{"title":"Hydrogen: A Novel Treatment Strategy in Kidney Disease","authors":"Bo Wang, Zhuoshu Li, Longfei Mao, Mingyi Zhao, Bingchang Yang, Xi Tao, Yuxiang Li, Guangming Yin","doi":"10.1159/000520981","DOIUrl":"https://doi.org/10.1159/000520981","url":null,"abstract":"Background: Hydrogen is a chemical substance that has yet to be widely used in medicine. However, recent evidence indicates that hydrogen has multi-faceted pharmacological effects such as antioxidant, anti-inflammatory, and antiapoptotic properties. An increased number of studies are being conducted on the application of hydrogen in various diseases, especially those affecting the renal system. Summary: Hydrogen can be inhaled, as a gas or liquid, and can be administered orally, intravenously, or locally. Hydrogen can rapidly enter suborganelles such as mitochondria and nucleus by simple diffusion, producing reactive oxygen species (ROS) and triggering DNA damage. Hydrogen can selectively scavenge hydroxyl radical (•OH) and peroxynitrite (ONOO−), but not other reactive oxygen radicals with physiological functions, such as peroxyanion (O2−) and hydrogen peroxide (H2O2). Although the regulatory effect of hydrogen on the signal transduction pathway has been confirmed, the specific mechanism of its influence on signal molecules remains unknown. Although many studies have investigated the therapeutic and preventive effects of H2 in cellular and animal experiments, clinical trials are few and still far behind. As a result, more clinical trials are required to investigate the role of hydrogen in kidney disease, as well as the effect of its dose, timing, and form on the overall efficacy. Large-scale randomized controlled clinical trials will be required before hydrogen can be used to treat renal illnesses. Key Messages: This article reviews the mechanisms of hydrogen in the treatment of renal disease and explores the possibilities of its use in clinical practice.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"155 1","pages":"126 - 136"},"PeriodicalIF":3.7,"publicationDate":"2022-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73446110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

History of Adverse Pregnancy on Subsequent Maternal-Fetal Outcomes in Patients with Immunoglobulin A Nephropathy: A Retrospective Cohort Study from a Chinese Single Center 不良妊娠史对免疫球蛋白A肾病患者后续母胎结局的影响:一项来自中国单中心的回顾性队列研究

IF 3.7 4区医学

Kidney Diseases Pub Date : 2021-12-09 DOI: 10.1159/000520586

Xingji Lian, L. Fan, Xin Ning, Cong Wang, Yi-fen Lin, Wenfang Chen, Wei Chen, Xueqing Yu

{"title":"History of Adverse Pregnancy on Subsequent Maternal-Fetal Outcomes in Patients with Immunoglobulin A Nephropathy: A Retrospective Cohort Study from a Chinese Single Center","authors":"Xingji Lian, L. Fan, Xin Ning, Cong Wang, Yi-fen Lin, Wenfang Chen, Wei Chen, Xueqing Yu","doi":"10.1159/000520586","DOIUrl":"https://doi.org/10.1159/000520586","url":null,"abstract":"Background: Gestation complications have a recurrence risk and could predispose to each other in the next pregnancy. We aimed to evaluate the relationship between a history of adverse pregnancy and maternal-fetal outcomes in subsequent pregnancy in patients with Immunoglobulin A nephropathy (IgAN). Methods: A retrospective cohort study from a Chinese single center was conducted. Pregnant women with biopsy-proven primary IgAN and aged ≥18 years were enrolled and divided into the 2 groups by a history of adverse pregnancy. The primary outcome was adverse pregnancy outcome, which included maternal-fetal outcomes. Logistical regression model was used to evaluate the association of a history of adverse pregnancy with subsequent adverse maternal and fetal outcomes. Results: Ninety-one women with 100 pregnancies were included, of which 54 (54%) pregnancies had a history of adverse pregnancy. IgAN patients with adverse pregnancy history had more composite maternal outcomes (70.4% vs. 45.7%, p = 0.012), while there was no difference in the composite adverse fetal outcomes between the 2 groups (55.6% vs. 45.7%). IgAN patients with a history of adverse pregnancy were associated with an increased risk of subsequent adverse maternal outcomes (adjusted odds ratio [OR], 2.64; 95% CI, 1.07–6.47). Similar results were shown in those with baseline serum albumin <3.5 g/dL, 24 h proteinuria ≥1 g/day, and a history of hypertension. There was no association between a history of adverse pregnancy and subsequent adverse fetal outcomes in IgAN patients (adjusted OR, 1.56; 95% CI, 0.63–3.87). Conclusion: A history of adverse pregnancy was associated with an increased risk of subsequent adverse maternal outcomes, but not for adverse fetal outcomes in IgAN patients.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"26 1","pages":"160 - 167"},"PeriodicalIF":3.7,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79359050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual-Specificity Phosphatases and Kidney Diseases 双特异性磷酸酶与肾脏疾病

IF 3.7 4区医学

Kidney Diseases Pub Date : 2021-12-01 DOI: 10.1159/000520142

Haiyang Li, Jiachuan Xiong, Yupei Du, Yinghui Huang, Jinghong Zhao

{"title":"Dual-Specificity Phosphatases and Kidney Diseases","authors":"Haiyang Li, Jiachuan Xiong, Yupei Du, Yinghui Huang, Jinghong Zhao","doi":"10.1159/000520142","DOIUrl":"https://doi.org/10.1159/000520142","url":null,"abstract":"Background: Dual-specificity phosphatases (DUSPs) belong to the family of protein tyrosine phosphatases, which can dephosphorylate both serine/threonine and tyrosine residues. During the past decades, DUSPs have been implicated in various physiological and pathological activities. Besides mitogen-activated protein kinases (MAPKs) as the main substrates, other protein and nonprotein substrates can also be dephosphorylated by DUSPs. Aberrant regulations of DUSPs have been found in various diseases such as cancer, neurological disorders, and kidney diseases, suggesting the involvement of DUSPs in the pathogenesis of diseases. Summary: In this review, we summarize the general characteristics of DUSPs and the research progress made in the field of kidney diseases, including diabetic nephropathy, hypertensive nephropathy, chronic kidney disease, acute kidney injury, and lupus nephritis. As the main biochemical function of DUSPs is to dephosphorylate MAPKs activity, decreased DUSPs are found in kidney disease models, whereas forced DUSPs expression reverses the disease presentation, which was proved by using transgenic or gene knockout model. Key Messages: Mounting evidence demonstrates that DUSPs have essential physiological and pathological functions in kidney disease. Fully understanding the functions and mechanisms of DUSPs in kidney disease contributes to their clinical application in translation medicine.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"13 1","pages":"13 - 25"},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78199210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury miR-125b通过靶向Mitofusin 1在顺铂诱导的急性肾损伤中破坏线粒体动力学

IF 3.7 4区医学

Kidney Diseases Pub Date : 2021-11-30 DOI: 10.1159/000520140

Yue-ru Zhao, Yue Lang, Mingchao Zhang, S. Liang, Xiaodong Zhu, Zhihong Liu

{"title":"miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury","authors":"Yue-ru Zhao, Yue Lang, Mingchao Zhang, S. Liang, Xiaodong Zhu, Zhihong Liu","doi":"10.1159/000520140","DOIUrl":"https://doi.org/10.1159/000520140","url":null,"abstract":"Background: Mitochondria are dynamic organelles whose structure are maintained by continuous fusion and fission. During acute kidney injury (AKI) progression, mitochondrial fission in renal tubular cells was elevated, characterized by mitochondrial fragmentation. It is tightly associated with mitochondrial dysfunction, which has been proven as a critical mechanism responsible for AKI. However, the initiating factor for the disruption of mitochondrial dynamics in AKI was not well understood. Objectives: To explore the molecular mechanisms of mitochondrial disorders and kidney damage. Methods: We established cisplatin-induced AKI model in C57BL/6 mice and proximal tubular cells, and detected the expression of miR-125b by qPCR. Then we delivered miR-125b antagomir after cisplatin treatment in mice via hydrodynamic-based gene transfer technique. Subsequently, we performed luciferase reporter and immunoblotting assays to prove miR-125b could directly modulate mitofusin1 (MFN1) expression. We also tested the role of miR-125b in mitochondrial and renal injury through immunofluorescent staining, qPCR, and immunoblotting assays. Results: miR-125b levels were induced in cisplatin-challenged mice and cultured tubular cells. Anti-miR-125b could effectively alleviate cisplatin-induced mitochondrial fragmentation and kidney injury both in vitro and in vivo. Furthermore, miR-125b could directly regulate MFN1, which is a key regulator of mitochondrial fusion. Our study indicated that miR-125b is upregulated during cisplatin-induced AKI. Inhibition of miR-125b may suppress mitochondrial and renal damage through upregulating MFN1. This study suggests that miR-125b could be a potential therapeutic target in AKI.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"59 1","pages":"137 - 147"},"PeriodicalIF":3.7,"publicationDate":"2021-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84273029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6