ArticlePloS one2012
Heparin-binding EGF-like growth factor induces heart interstitial fibrosis via an Akt/mTor/p70s6k pathway.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Identification of epigenetic regulators of fibrotic transformation in cardiac fibroblasts through bulk and single-cell CRISPR screens.Nature communications · 2025Article
- QSOX2-Mediated Disulfide Bond Modification Enhances Tumor Stemness and Chemoresistance by Activating TSC2/mTOR/c-Myc Feedback Loop in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unraveling the heart-brain axis: shared genetic mechanisms in cardiovascular diseases and Schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- HB-EGF Plasmatic Level Contributes to the Development of Early Risk Prediction Nomogram for Severe COVID-19 Cases.Biomedicines · 2024Article
- DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts.Nature communications · 2024Article
- Article
- Single-Dose Treatment with Rapamycin Preserves Post-Ischemic Cardiac Function through Attenuation of Fibrosis and Inflammation in Diabetic Rabbit.International journal of molecular sciences · 2023Article
- Identifying Genes Related to Acute Myocardial Infarction Based on Network Control Capability.Genes · 2022Article
- EGF Contributes to Hypertrophy of Human Ligamentum Flavum via the TGF-β1/Smad3 Signaling Pathway.International journal of medical sciences · 2022Article
- Yes-Associated Protein (Yap) Is Up-Regulated in Heart Failure and Promotes Cardiac Fibroblast Proliferation.International journal of molecular sciences · 2021Article
- Angiogenesis and angiocrines regulating heart growth.Vascular biology (Bristol, England) · 2020Review
- Maternal High Fat Diet and Diabetes Disrupts Transcriptomic Pathways That Regulate Cardiac Metabolism and Cell Fate in Newborn Rat Hearts.Frontiers in endocrinology · 2020Article
- Soluble Heparin Binding Epidermal Growth Factor-Like Growth Factor Is a Regulator ofMolecular and cellular biology · 2019Article
- New Noonan syndrome model mice with RIT1 mutation exhibit cardiac hypertrophy and susceptibility to β-adrenergic stimulation-induced cardiac fibrosis.EBioMedicine · 2019Article
- Clinical Prescription-Protein-Small Molecule-Disease Strategy (CPSD), A New Strategy for Chinese Medicine Development: A Case Study in Cardiovascular Diseases.Frontiers in pharmacology · 2019Article
- New Insights Into the Role of mTOR Signaling in the Cardiovascular System.Circulation research · 2018Review
- T3 peptide, a fragment of tumstatin, stimulates proliferation and migration of cardiac fibroblasts through activation of Akt signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Nitrite Prevents Right Ventricular Failure and Remodeling Induced by Pulmonary Artery Banding.Journal of cardiovascular pharmacology · 2017Article
- Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II.Hypertension (Dallas, Tex. : 1979) · 2016Article
- ADAM17 substrate release in proximal tubule drives kidney fibrosis.JCI insight · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is essential for maintaining normal function of the adult heart and is known to play an important role in myocardial remodeling. In the present study, we observed that heart-specific HB-EGF transgenic (TG) mice had systolic dysfunction with decreased fractional shortening (FS%), increased end-systolic diameter (LVIDs) at 5 months of age, increased heart fibrosis, and increased mRNA expression of Col1α1 and Col3α1 at 1, 3, 5 and 7 months of age compared to nontransgenic (NTG) littermates. However, the left ventricular anterior wall thickness at end-systole (LVAWs) of the TG mice was not different than the NTG mice. Phosphorylation levels of Akt, mTor and p70s6k were increased due to HB-EGF expression in TG mice compared with the NTG mice at 3 and 7 months of age. Additionally, activated Akt, mTor and p70s6k were co-localized with vimentin to cardiac fibroblasts isolated from TG mice. Furthermore, HB-EGF significantly increased phosphorylation levels of Akt, mTor and p70s6k and increased expression of type I collagen in cultured primary cardiac fibroblasts. Rapamycin (Rapa) and CRM197, inhibitors of mTor and HB-EGF respectively, could inhibit the expression of type I collagen in the cultured primary cardiac fibroblasts and Rapa suppressed interstitial fibrosis of the heart tissues in vivo. In addition, a BrdU assay showed that HB-EGF increased proliferation of cardiac fibroblasts by 30% compared with cells without HB-EGF treatment. HB-EGF-induced proliferation was completely diminished in the presence of Rapa. These results suggest that HB-EGF induced heart fibrosis and proliferation of cardiac fibroblasts occurs through activation of the Akt/mTor/p70s6k pathway.
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