Journal of The American Society of Nephrology最新文献

{"title":"Role of ZBP1 Sensing Mitochondrial Z-DNA and triggering Necroptosis in Oxalate-Induced Acute Kidney Injury.","authors":"Caiming Chen,Jingzhi Xie,Zhimin Chen,Keng Ye,Chengkun Wu,Xingchen Dai,Ying Yuan,Yujiao Lin,Yujia Wang,Hong Chen,Jianfeng Wu,Huabin Ma,Yanfang Xu","doi":"10.1681/asn.0000000516","DOIUrl":"https://doi.org/10.1681/asn.0000000516","url":null,"abstract":"BACKGROUNDCalcium oxalate-induced acute kidney injury is a severe condition in which the kidneys suffer rapid damage due to the deposition of oxalate crystals. Known factors contributing to cell death induced by calcium oxalate include receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) protein dependent necroptosis, as well as necrosis involving peptidylprolyl isomerase F (PPIF) mediated mitochondrial permeability transition. However, the detailed molecular mechanisms linking mitochondrial dysfunction to RIPK3 activation are not fully understood.METHODSMice with gene knock-out of Zbp1, Ripk3, or Mlkl and mice with mutations in the Z-nucleic acid sensing domain of ZBP1 or deletion of Zα1 were used in an oxalate-induced AKI model. Proximal renal tubule cells were isolated and cultured for further investigation. Human oxalate nephropathy biopsy samples were analyzed.RESULTSSpecific gene deletions of Zbp1, Ripk3, or Mlkl in proximal renal tubules significantly reduced the severity of oxalate-induced AKI by preventing necroptosis and subsequent inflammation. Notably, mice with mutations in the Z-nucleic acid sensing domain of ZBP1 or deletion of Zα1 were protected from AKI. In cultured proximal tubular cells, calcium oxalate damaged mitochondria, accompanied by an increase in Bax and a decrease in BCL2 and TAFM, leading to the release of mitochondrial Z-DNA. ZBP1 sensed this mitochondrial Z-DNA and then recruited RIPK3 via the RIP homotypic interaction motifs (RHIM), which in turn activated MLKL through RIPK3 phosphorylation, leading to necroptosis and contributing to AKI.CONCLUSIONSZBP1 plays a critical role in sensing mitochondrial Z-DNA and initiating RIPK3/MLKL-mediated necroptosis, contributing to the development of oxalate-induced AKI.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"66 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-Mediated N 6 -Methyladenosine mRNA Modification and cGAS-STING Pathway Activity in Kidney Fibrosis.","authors":"Yu-Cheng Tsai, Tsung-Han Hsieh, Yuan-Ru Liao, Ming-Tsun Tsai, Tzu-Ping Lin, Der-Yen Lee, Jihwan Park, Donggun Kim, Katalin Susztak, Shang-Feng Yang, Chih-Ching Lin, Szu-Yuan Li","doi":"10.1681/ASN.0000000000000428","DOIUrl":"10.1681/ASN.0000000000000428","url":null,"abstract":"<p><strong>Background: </strong>Chemical modifications on RNA profoundly affect RNA function and regulation. m6A, the most abundant RNA modification in eukaryotes, plays a pivotal role in diverse cellular processes and disease mechanisms. However, its importance is understudied in human CKD samples regarding its influence on pathological mechanisms.</p><p><strong>Methods: </strong>Liquid chromatography–tandem mass spectrometry and methylated RNA immunoprecipitation sequencing were used to examine alterations in m6A levels and patterns in CKD samples. Overexpression of the m6A writer METTL3 in cultured kidney tubular cells was performed to confirm the effect of m6A in tubular cells and explore the biological functions of m6A modification on target genes. In addition, tubule-specific deletion of Mettl3 (Ksp-Cre Mettl3f/f) mice and antisense oligonucleotides inhibiting Mettl3 expression were used to reduce m6A modification in an animal kidney disease model.</p><p><strong>Results: </strong>By examining 127 human CKD samples, we observed a significant increase in m6A modification and METTL3 expression in diseased kidneys. Epitranscriptomic analysis unveiled an enrichment of m6A modifications in transcripts associated with the activation of inflammatory signaling pathways, particularly the cyclic guanosine monophosphate–AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway. m6A hypermethylation increased mRNA stability in cGAS and STING1 as well as elevated the expression of key proteins within the cGAS-STING pathway. Both the tubule-specific deletion of Mettl3 and the use of antisense oligonucleotides to inhibit Mettl3 expression protected mice from inflammation, reduced cytokine expression, decreased immune cell recruitment, and attenuated kidney fibrosis.</p><p><strong>Conclusions: </strong>Our research revealed heightened METTL3-mediated m6A modification in fibrotic kidneys, particularly enriching the cGAS-STING pathway. This hypermethylation increased mRNA stability for cGAS and STING1, leading to sterile inflammation and fibrosis.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"35 10","pages":"1312-1329"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glomerular Endothelial Cell Receptor Adhesion G-Protein-Coupled Receptor F5 (ADGRF5) and the Integrity of the Glomerular Filtration Barrier.","authors":"Miki Nagase, Hikaru Ando, Yoshiaki Beppu, Hidetake Kurihara, Souta Oki, Fumimasa Kubo, Kazuki Yamamoto, Takashi Nagase, Shinya Kaname, Yoshihiro Akimoto, Hiroshi Fukuhara, Tatsuo Sakai, Shigehisa Hirose, Nobuhiro Nakamura","doi":"10.1681/ASN.0000000000000427","DOIUrl":"10.1681/ASN.0000000000000427","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1366-1380"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Plasma Metabolome and Risk of Incident Kidney Stones.","authors":"Pietro Manuel Ferraro, Yukun Li, Raji Balasubramanian, Gary C Curhan, Eric N Taylor","doi":"10.1681/ASN.0000000000000421","DOIUrl":"10.1681/ASN.0000000000000421","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1412-1421"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in Olfactory and Cognitive Function after Kidney Transplantation.","authors":"Aditi Gupta, Parker Holloway, Kate Young, Jennifer Villwock, Robert Montgomery","doi":"10.1681/ASN.0000000000000456","DOIUrl":"10.1681/ASN.0000000000000456","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1422-1424"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solitary Kidney Seeks Potassium Alkali to Lower the Pressure.","authors":"Cary R Boyd-Shiwarski, Aylin R Rodan","doi":"10.1681/ASN.0000000000000476","DOIUrl":"10.1681/ASN.0000000000000476","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1300-1302"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Acute Declines in eGFR during Renin-Angiotensin System Inhibition and Risk of Adverse Outcomes.","authors":"Elaine Ku, Hocine Tighiouart, Charles E McCulloch, Lesley A Inker, Ogechi M Adingwupu, Tom Greene, Raymond O Estacio, Mark Woodward, Dick de Zeeuw, Julia B Lewis, Thierry Hannedouche, Fan Fan Hou, Tazeen H Jafar, Enyu Imai, Giuseppe Remuzzi, Hiddo J L Heerspink, Robert D Toto, Mark J Sarnak","doi":"10.1681/ASN.0000000000000426","DOIUrl":"10.1681/ASN.0000000000000426","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1402-1411"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authors' Reply: Utility of Urinary CD4 + T-Cell Count in Detecting ANCA-Associated Vasculitis Renal Relapse.","authors":"Luka Prskalo, Adrian Schreiber, Philipp Enghard","doi":"10.1681/ASN.0000000000000408","DOIUrl":"10.1681/ASN.0000000000000408","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1452"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-Glucose Cotransporter 2 Inhibitors in Older Patients with CKD.","authors":"Wisanne M Bakker, Ron T Gansevoort, Changyuan Yang, Glenn M Chertow, Hiddo J L Heerspink, Priya Vart","doi":"10.1681/ASN.0000000000000466","DOIUrl":"10.1681/ASN.0000000000000466","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1446-1449"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2Y2R and Cyst Growth in Polycystic Kidney Disease.","authors":"Andre Kraus, Kathrin Skoczynski, Martin Brötsch, Nicolai Burzlaff, Jens Leipziger, Mario Schiffer, Maike Büttner-Herold, Bjoern Buchholz","doi":"10.1681/ASN.0000000000000416","DOIUrl":"10.1681/ASN.0000000000000416","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"1351-1365"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}