ArticleNature medicine2012
A systems approach identifies HIPK2 as a key regulator of kidney fibrosis.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 156 citations in OpenAlex.
- Shared and Tissue-Specific Expression Signatures between Bone Marrow from Primary Myelofibrosis and Essential Thrombocythemia.Experimental hematology · 2019Trial
- Modelling ischaemic AKI in human kidney organoids reveals injury-associated epithelial states and macrophage-epithelial crosstalk.Genome medicine · 2026Article
- Cardiomyocytes HIPK2 regulates myocardial inflammation and heart function through purinergic signaling.Cell communication and signaling : CCS · 2026Article
- TGF-β in chronic kidney disease: a controversy for decades.Frontiers in immunology · 2026Review
- New potential therapeutic targets of metabolic disorder-associated kidney disease and diabetic kidney disease.Kidney international · 2026Review
- The Evolution of Systems Biology and Systems Medicine: From Mechanistic Models to Uncertainty Quantification.Annual review of biomedical engineering · 2025Review
- Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.Circulation research · 2025Article
- Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.International journal of biological sciences · 2025Review
- Virtual Screening, Molecular Dynamics, and Mechanism Study of Homeodomain-Interacting Protein Kinase 2 Inhibitor in Renal Fibroblasts.Pharmaceuticals (Basel, Switzerland) · 2024Article
- 1,25(OH)Endocrine · 2024Article
- PKR activation-induced mitochondrial dysfunction in HIV-transgenic mice with nephropathy.eLife · 2024Article
- Multiomics2Targets identifies targets from cancer cohorts profiled with transcriptomics, proteomics, and phosphoproteomics.Cell reports methods · 2024Article
- Small Molecule Allosteric Inhibitor of HIPK2 as a Novel Therapy against Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2024Article
- Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis.The Journal of clinical investigation · 2024Article
- HIPK2 C-terminal domain inhibits NF-κB signaling and renal inflammation in kidney injury.JCI insight · 2024Article
- The occurrence and development mechanisms of esophageal stricture: state of the art review.Journal of translational medicine · 2024Review
- The Sweet Side of HIPK2.Cancers · 2023Review
- Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.Progress in retinal and eye research · 2023Review
- HIPK2 as a Novel Regulator of Fibrosis.Cancers · 2023Review
- ASH2L Aggravates Fibrosis and Inflammation through HIPK2 in High Glucose-Induced Glomerular Mesangial Cells.Genes · 2022Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Kidney fibrosis is a common process that leads to the progression of various types of kidney disease. We used an integrated computational and experimental systems biology approach to identify protein kinases that regulate gene expression changes in the kidneys of human immunodeficiency virus (HIV) transgenic mice (Tg26 mice), which have both tubulointerstitial fibrosis and glomerulosclerosis. We identified homeo-domain interacting protein kinase 2 (HIPK2) as a key regulator of kidney fibrosis. HIPK2 was upregulated in the kidneys of Tg26 mice and in those of patients with various kidney diseases. HIV infection increased the protein concentrations of HIPK2 by promoting oxidative stress, which inhibited the seven in absentia homolog 1 (SIAH1)-mediated proteasomal degradation of HIPK2. HIPK2 induced apoptosis and the expression of epithelial-to-mesenchymal transition markers in kidney epithelial cells by activating the p53, transforming growth factor β (TGF-β)-SMAD family member 3 (Smad3) and Wnt-Notch pathways. Knockout of HIPK2 improved renal function and attenuated proteinuria and kidney fibrosis in Tg26 mice, as well as in other murine models of kidney fibrosis. We therefore conclude that HIPK2 is a potential target for anti-fibrosis therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.