ArticleGenes & genomics2019
Human epididymis protein 4 (HE4) protects against cystic pulmonary fibrosis associated-inflammation through inhibition of NF-κB and MAPK singnaling.
Article in Genes & genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Serum HE4 and polymorphisms in MMP9 and MMP13 associated with survival outcome in patients with endometrial carcinoma: a retrospective cohort study and nomogram development.Future science OA · 2026Article
- Human epididymis protein 4: a potential prognostic biomarker for rheumatoid arthritis-associated interstitial lung disease.Clinical rheumatology · 2026Article
- Plasma level of human epididymis protein 4 is associated with risk of future venous thromboembolism-the Trøndelag Health study.Journal of thrombosis and haemostasis : JTH · 2026Article
- Inflammatory Markers and Microbiome Dysbiosis in Hematopoietic Cell Transplant Recipients with Lung Graft-versus-Host Disease.Transplantation and cellular therapy · 2025Article
- Human epididymis protein 4-annexin II binding promotes aberrant epithelial-fibroblast crosstalk in pulmonary fibrosis.Communications biology · 2025Article
- Silencing HE4 alleviates the renal fibrosis in lupus nephritis mice by regulating the C3/MMPs/prss axis.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Diagnostic value of cerebrospinal fluid human epididymis protein 4 for leptomeningeal metastasis in lung adenocarcinoma.Frontiers in immunology · 2024Article
- Prognostic Value of Human Epididymis Protein 4 in Acute Myocardial Infarction.International journal of general medicine · 2024Article
- The Role of MMPs in the Era of CFTR Modulators: An Additional Target for Cystic Fibrosis Patients?Biomolecules · 2023Review
- Elevation of serum human epididymis protein 4 (HE4) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as predicting factors for the occurrence of acute kidney injury on chronic kidney disease: a single-center retrospective self-control study.Frontiers in pharmacology · 2023Article
- Human epididymis protein 4 aggravates airway inflammation and remodeling in chronic obstructive pulmonary disease.Respiratory research · 2022Article
- Danggui Buxue Tang Ameliorates Bleomycin-Induced Pulmonary Fibrosis by Suppressing the TLR4/NLRP3 Signaling Pathway in Rats.Evidence-based complementary and alternative medicine : eCAM · 2021Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCystic pulmonary fibrosis (CF) affects mostly the lung of the newborns. Chronic infection and inflammation become the major causes of morbidity and mortality in CF. However, the underlying molecular mechanisms causing CF still remain unclear.
methodsELISA assay was used to examine the expression of HE4 and pro-inflammatory cytokines in W126VA4 cells supernatant fluid. qRT-PCR was applicable to determine the mRNA level of HE4, α-SMA, collagen 1, MMP2, MMP9 and various interleukins. Immunofluorescent assay was used to test the expression of HE4 in WI-26 VA4 cells. Major elements of MAPK and NF-κB signals pathways were examined by western blot.
resultsWe found higher expression of HE4 in CF patients serum and lung biopsy. Interestingly, HE4 expression was positively correlated with fibrosis markers expression. In addition,HE4 overexpression increased inflammatory cytokines secretion and fibrosis markers expression in WI-26 VA4 cells. And NF-κB pathways were responsible for elevated inflammation. In addition, HE4/MAPK/MMPs signaling cascades destroyed the normal extracellular matrix (ECM) and promoted fibrosis.
conclusionsOverall, we first identified that HE4 promoted CF-associated inflammation. Additionally, NF-κB and MAPK signalings were further validated to be responsible for CF-associated inflammation and ECM destruction. Characterization of lumacaftor/ivacaftor in CF-associated inflammation may provide a novel insight into clinical CF treatment.
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