{"title":"Let Food Be Thy Medicine: Potential of Dietary Management in Cystinosis.","authors":"Elena Levtchenko, Fanny Oliveira Arcolino","doi":"10.1681/ASN.0000000509","DOIUrl":"https://doi.org/10.1681/ASN.0000000509","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":null,"pages":null},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349097","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}
Pub Date : 2024-10-01Epub Date: 2024-06-10DOI: 10.1681/ASN.0000000000000428
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
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
{"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":null,"pages":null},"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}
Pub Date : 2024-10-01Epub Date: 2024-06-12DOI: 10.1681/ASN.0000000000000421
Pietro Manuel Ferraro, Yukun Li, Raji Balasubramanian, Gary C Curhan, Eric N Taylor
{"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":null,"pages":null},"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}
Pub Date : 2024-10-01Epub Date: 2024-06-18DOI: 10.1681/ASN.0000000000000426
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
{"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":null,"pages":null},"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}
Pub Date : 2024-10-01Epub Date: 2024-07-02DOI: 10.1681/ASN.0000000000000456
Aditi Gupta, Parker Holloway, Kate Young, Jennifer Villwock, Robert Montgomery
{"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":null,"pages":null},"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}
Pub Date : 2024-10-01Epub Date: 2024-08-21DOI: 10.1681/ASN.0000000000000476
Cary R Boyd-Shiwarski, Aylin R Rodan
{"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":null,"pages":null},"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}
Pub Date : 2024-10-01Epub Date: 2024-06-06DOI: 10.1681/ASN.0000000000000408
Luka Prskalo, Adrian Schreiber, Philipp Enghard
{"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":null,"pages":null},"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}
Pub Date : 2024-10-01Epub Date: 2024-06-07DOI: 10.1681/ASN.0000000000000416
Andre Kraus, Kathrin Skoczynski, Martin Brötsch, Nicolai Burzlaff, Jens Leipziger, Mario Schiffer, Maike Büttner-Herold, Bjoern Buchholz
{"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":null,"pages":null},"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}
Pub Date : 2024-10-01Epub Date: 2024-07-29DOI: 10.1681/ASN.0000000000000466
Wisanne M Bakker, Ron T Gansevoort, Changyuan Yang, Glenn M Chertow, Hiddo J L Heerspink, Priya Vart
{"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":null,"pages":null},"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}
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