ArticleCell metabolism2021
The Nuclear Receptor ESRRA Protects from Kidney Disease by Coupling Metabolism and Differentiation.
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Article in Cell metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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117citing papers in PubMed
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Who cites it
117 citing papers in PubMed, 166 citations in OpenAlex.
- Systematic production of human kidney organoids for transplantation in porcine kidneys during ex vivo machine perfusion.Nature biomedical engineering · 2026Article
- Matrix Gla Protein is a novel regulator of TGFβ-dependent fibroblast activation and kidney fibrosis.Molecular biomedicine · 2026Article
- The nuclear receptor ESRRA is a crucial regulator of acute kidney injury through inhibition of the lipophagy-ferroptosis axis.Autophagy · 2026Article
- ELF3 links kidney function GWAS loci to maladaptive epithelial inflammation.Science advances · 2026Article
- Single-cell RNA sequencing and spatial transcriptomics in the discovery of kidney disease potential biomarkers: a narrative review.BMC nephrology · 2026Review
- ERRγ deletion in podocytes accelerates aging related kidney disease.bioRxiv : the preprint server for biology · 2026Article
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Increased WNT10B/FOXO6 signaling promotes cell fate transition in renal tubular cells to aggravate renal inflammation and fibrosis.Nature communications · 2026Article
- Pyruvate Dehydrogenase and Cellular Metabolism in Calcineurin Inhibitor-Induced Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2026Article
- Hyperlipidemia in membranous nephropathy.Clinical kidney journal · 2026Review
- Lipids in kidney diseases: from systemic imbalance to intrarenal alterations of cellular lipid metabolism in rare and common kidney diseases.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Fatty acid metabolism: opportunities and challenges of traditional Chinese medicine in the treatment of renal fibrosis.Chinese medicine · 2026Review
- Shen-Shuai-II-Recipe inhibits aerobic glycolysis through SIRT1 in 5/6 ablation/infarction renal failure model.Scientific reports · 2026Article
- Therapeutic remodeling of the ceramide backbone prevents kidney injury.Cell metabolism · 2026Article
- Injured proximal tubule-driven paracrine signaling promotes lipid-associated macrophage expansion and chondroitin sulfate biosynthesis via PPARG/TCF12 in diabetic kidney disease.Frontiers in immunology · 2026Article
- Precision Nanomedicine for Renal Tubular Injury: From Passive Accumulation to Subcellular Targeting.International journal of nanomedicine · 2026Review
- The double-edged sword effect of estrogen in kidney disease and its precision modulation.Frontiers in endocrinology · 2026Review
- Elovl7 sensitizes podocytes to ferroptosis in podocytopathy by elongating polyunsaturated fatty acids.Cell death & disease · 2025Article
- The nonsteroidal MR antagonist finerenone reverses Western diet-induced kidney disease by regulating mitochondrial and lipid metabolism and inflammation.American journal of physiology. Renal physiology · 2025Article
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
57 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 5 institutions in 3 countries.
Poonam DhillonRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Jihwan ParkRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju, Republic of Korea. Electronic address: jihwan.park@gist.ac.kr.
Carmen Hurtado Del PozoPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Technology (BIST), Barcelona, Spain.
Lingzhi LiRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Tomohito DokeRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Shizheng HuangRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Juanjuan ZhaoCenter for Mitochondrial and Epigenomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hyun Mi KangRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Laboratory of Disease Modeling and Therapeutics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Rojesh ShrestraRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Michael S BalzerRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Shatakshee ChatterjeeRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Patricia PradoPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Technology (BIST), Barcelona, Spain.
Seung Yub HanDepartment of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hongbo LiuRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Xin ShengRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Pieterjan DierickxInstitute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Kirill BatmanovRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Juan P RomeroCell Therapy Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Oncohematology Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Hematology and Area of Cell Therapy, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.
Felipe PrósperCell Therapy Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Oncohematology Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain; Hematology and Area of Cell Therapy, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.
Mingyao LiDepartment of Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Liming PeiInstitute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Center for Mitochondrial and Epigenomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Junhyong KimDepartment of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nuria MontserratPluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Technology (BIST), Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Madrid, Spain. Electronic address: nmontserrat@ibecbarcelona.eu.
Katalin SusztakRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: ksusztak@pennmedicine.upenn.edu.
University of Pennsylvania · USInstitute for Bioengineering of Catalonia · ESUniversidad de Navarra · ESGwangju Institute of Science and Technology · KRInstitució Catalana de Recerca i Estudis Avançats · ES
Funding
VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Patrick Seale · 1986 to 2026
$48.3MRole of the Notch Pathway in Kidney InjuryR01DK076077 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATALIN SUSZTAK · 2007 to 2026
$8.0MEpigenetics of Chronic Kidney DiseaseR01DK087635 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATALIN SUSZTAK · 2009 to 2026
$7.0MAPOL1 associated kidney diseaseR01DK105821 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SUSZTAK, KATALIN · 2016 to 2024
$4.6MEpigenetic drivers and biomarkers of diabetic kidney diseaseDP3DK108220 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SUSZTAK, KATALIN · 2015 to 2015
$2.4MCoordinated regulation of mitochondrial and cellular functions by nuclear receptorsR01DK111495 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI PEI, LIMING · 2017 to 2021
$2.0MThe role of cytosolic nucleotide sensors in inflammatory fibrosisR01DK132630 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SUSZTAK, KATALIN · 2022 to 2025
$2.0MNIDDK NIH HHS DP3 DK108220NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK076077NIDDK NIH HHS R01 DK087635NIDDK NIH HHS R01 DK105821NIDDK NIH HHS R01 DK111495NIDDK NIH HHS R01 DK132630
Abstract
Kidney disease is poorly understood because of the organ's cellular diversity. We used single-cell RNA sequencing not only in resolving differences in injured kidney tissue cellular composition but also in cell-type-specific gene expression in mouse models of kidney disease. This analysis highlighted major changes in cellular diversity in kidney disease, which markedly impacted whole-kidney transcriptomics outputs. Cell-type-specific differential expression analysis identified proximal tubule (PT) cells as the key vulnerable cell type. Through unbiased cell trajectory analyses, we show that PT cell differentiation is altered in kidney disease. Metabolism (fatty acid oxidation and oxidative phosphorylation) in PT cells showed the strongest and most reproducible association with PT cell differentiation and disease. Coupling of cell differentiation and the metabolism was established by nuclear receptors (estrogen-related receptor alpha [ESRRA] and peroxisomal proliferation-activated receptor alpha [PPARA]) that directly control metabolic and PT-cell-specific gene expression in mice and patient samples while protecting from kidney disease in the mouse model.
Indexed as
AnimalsCell DifferentiationCells, CulturedERRalpha Estrogen-Related ReceptorKidney DiseasesMaleMiceMice, Inbred C57BLMice, KnockoutReceptors, EstrogenERRalpha Estrogen-Related ReceptorReceptors, Estrogenchronic kidney diseaseESRRAfatty-acid oxidationfibrosiskidneyorganoidsPPARAproximal tubule cellssingle-cell ATAC sequencingsingle-cell RNA sequencing
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