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Protective role for kidney TREM2high macrophages in obesity- and diabetes-induced kidney injury.
Subramanian, Ayshwarya; Vernon, Katherine A; Zhou, Yiming; Marshall, Jamie L; Alimova, Maria; Arevalo, Carlos; Zhang, Fan; Slyper, Michal; Waldman, Julia; Montesinos, Monica S; Dionne, Danielle; Nguyen, Lan T; Cuoco, Michael S; Dubinsky, Dan; Purnell, Jason; Keller, Keith; Sturner, Samuel H; Grinkevich, Elizabeth; Ghoshal, Ayan; Kotek, Amanda; Trivioli, Giorgio; Richoz, Nathan; Humphrey, Mary B; Darby, Isabella G; Miller, Sarah J; Xu, Yingping; Weins, Astrid; Chloe-Villani, Alexandra; Chang, Steven L; Kretzler, Matthias; Rosenblatt-Rosen, Orit; Shaw, Jillian L; Zimmerman, Kurt A; Clatworthy, Menna R; Regev, Aviv; Greka, Anna.
Afiliação
  • Subramanian A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: as3894@cornell.edu.
  • Vernon KA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zhou Y; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: zhouym35@mail.sysu.edu.cn.
  • Marshall JL; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Alimova M; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Arevalo C; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zhang F; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Slyper M; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Waldman J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Montesinos MS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Dionne D; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Nguyen LT; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Cuoco MS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Dubinsky D; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Purnell J; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Keller K; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Sturner SH; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Grinkevich E; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ghoshal A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kotek A; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Trivioli G; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK; Nephrology Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • Richoz N; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
  • Humphrey MB; Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Darby IG; Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Miller SJ; Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Xu Y; Institute of Dermatology and Venereology, Dermatology Hospital, Southern Medical University, Guangzhou, China.
  • Weins A; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Chloe-Villani A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chang SL; Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, MA, USA; Division of Urology, Brigham and Women's Hospital, Boston, MA, USA.
  • Kretzler M; Internal Medicine, Department of Nephrology, University of Michigan, Ann Arbor, MI, USA.
  • Rosenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Shaw JL; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zimmerman KA; Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Clatworthy MR; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK; Cellular Genetics, Wellcome Sanger Institute, Hinxton, UK; NIHR Cambridge Biomedical Research Center, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Cambridge, UK.
  • Regev A; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Greka A; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Kidney Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: agreka@broadinstitute.org.
Cell Rep ; 43(6): 114253, 2024 Jun 25.
Article em En | MEDLINE | ID: mdl-38781074
ABSTRACT
Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression-high-fat diet (HFD)-fed mice aged to 90-100 weeks and BTBR ob/ob mice (a genetic model)-and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Receptores Imunológicos / Camundongos Knockout / Nefropatias Diabéticas / Dieta Hiperlipídica / Rim / Macrófagos / Obesidade Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glicoproteínas de Membrana / Receptores Imunológicos / Camundongos Knockout / Nefropatias Diabéticas / Dieta Hiperlipídica / Rim / Macrófagos / Obesidade Idioma: En Ano de publicação: 2024 Tipo de documento: Article