ArticleNature medicine2013
Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.
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Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Potential association between elevated serum human epididymis protein 4 and renal fibrosis: A systemic review and meta-analysis.Medicine · 2017Pooled it
- Human Epididymis Protein 4 in Cardiovascular Disease: A Fibrosis-Driven Mediator of Tissue Remodeling and Inter-Organ Communication.Circulation reports · 2026Review
- Human epididymis protein 4 is a predictor of long-term mortality and major adverse cardiovascular events in patients with coronary artery disease.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Glycemic status-dependent proteomic signatures of biological aging for health risk prediction.GeroScience · 2026Article
- Serum human epididymis protein 4 and long-term mortality in U.S. women: a nationally representative cohort study.Clinics (Sao Paulo, Brazil) · 2026Article
- Human epididymis protein 4: a potential prognostic biomarker for rheumatoid arthritis-associated interstitial lung disease.Clinical rheumatology · 2026Article
- The course of platinum-based chemotherapy is associated with the risk of hematological complications during poly(ADP-ribose) polymerase (PARP) inhibitor therapy in patients with ovarian cancer.Pharmacological reports : PR · 2026Article
- Amiloride mitigates respiratory distress caused by WFDC2 deficiency via inhibiting the epithelial sodium channel.Nature communications · 2026Article
- Renal IGFBP6 Interacts With THBS1 to Drive Renal Cellular Senescence and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Astaxanthin Alleviates Bleomycin-Induced Pulmonary Fibrosis in Mice by Suppressing the Fibroblast-to-Myofibroblast Transition and Collagen Deposition.Molecular nutrition & food research · 2026Article
- Proteomic risk score for early prediction of kidney disease progression in individuals with APOL1 high-risk genotypes.Nature medicine · 2026Article
- HE4 drives PD-L1 expression in myeloid cells via IFN-γR-JAK-STAT3 signaling to promote tumor immune evasion.Cell reports. Medicine · 2026Article
- Skin capillary endothelial cells form a network of spatiotemporally conserved CabioRxiv : the preprint server for biology · 2026Article
- Spatial and Single-Cell Transcriptomics Reveal Keratinocytes as Key Players in Vulvar Lichen Sclerosus Pathogenesis.The Journal of investigative dermatology · 2026Article
- Chronic kidney disease onset, progression, and cardiovascular outcomes: proteomics informs biology and risk stratification.Cardiovascular diabetology · 2026Article
- HE4: a potential diagnostic biomarker in autoimmune diseases.Central-European journal of immunology · 2026Review
- Improved sex-specific cardiovascular risk prediction with multi-omics data in people with type 2 diabetes.Cardiovascular diabetology · 2025Article
- Exploratory Study of Prognostic Plasma Biomarkers in Patients with Pulmonary Arterial Hypertension.The American journal of pathology · 2025Article
- Hypoxia-Induced Metabolic Reprogramming and Markings of Cell Fate in Concentric Arterial Hypertrophy.bioRxiv : the preprint server for biology · 2025Article
- Human epididymis protein 4-annexin II binding promotes aberrant epithelial-fibroblast crosstalk in pulmonary fibrosis.Communications biology · 2025Article
79 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
The functional contribution of myofibroblasts in fibrosis is not well understood. Using a new genetic mouse model to track and isolate myofibroblasts, we performed gene expression profiling followed by biological validation to identify HE4 (encoding human epididymis protein 4, also known as WAP 4-disulfide core domain-2 or Wfdc2) as the most upregulated gene in fibrosis-associated myofibroblasts. The HE4 gene encodes for a putative serine protease inhibitor that is upregulated in human and mouse fibrotic kidneys and is elevated in the serum of patients with kidney fibrosis. HE4 suppresses the activity of multiple proteases, including serine proteases and matrix metalloproteinases, and specifically inhibits their capacity to degrade type I collagen. In particular, we identified two serine proteases, Prss35 and Prss23, as HE4 targets with functional relevance in kidney fibrosis. Administration of HE4-neutralizing antibodies accelerated collagen I degradation and inhibited fibrosis in three different mouse models of renal disease. Collectively these studies suggest that HE4 is a potential biomarker of renal fibrosis and a new therapeutic target.
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