ArticleJournal of molecular medicine (Berlin, Germany)2018
PHP14 regulates hepatic stellate cells migration in liver fibrosis via mediating TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway.
Article in Journal of molecular medicine (Berlin, Germany), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 31 citations in OpenAlex.
- PHPT1 acts as an inhibitor in high-altitude pulmonary hypertension via negative TRPV5 signaling regulation.Journal of translational medicine · 2025Article
- Histidine Phosphorylation: Protein Kinases and Phosphatases.International journal of molecular sciences · 2024Review
- The role of lncRNA-mediated ceRNA regulatory networks in liver fibrosis.Non-coding RNA research · 2024Review
- Clinical and molecular characteristics of Jordanian oropharyngeal cancer patients according to P16 expression: a retrospective study and a report of a novel biomarker.Medical molecular morphology · 2024Article
- Angelica dahurica extract and its effective component bergapten alleviated hepatic fibrosis by activating FXR signaling pathway.Journal of natural medicines · 2024Article
- FBXO32 targets PHPT1 for ubiquitination to regulate the growth of EGFR mutant lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Ferulic Acid Combined With Bone Marrow Mesenchymal Stem Cells Attenuates the Activation of Hepatic Stellate Cells and Alleviates Liver Fibrosis.Frontiers in pharmacology · 2022Article
- Bellidifolin Ameliorates Isoprenaline-Induced Myocardial Fibrosis by Regulating TGF-β1/Smads and p38 Signaling and Preventing NR4A1 Cytoplasmic Localization.Frontiers in pharmacology · 2021Article
- The Small GTPase RAC1B: A Potent Negative Regulator of-and Useful Tool to Study-TGFβ Signaling.Cancers · 2020Review
- Screening and evaluation of key genes in contributing to pathogenesis of hepatic fibrosis based on microarray data.European journal of medical research · 2020Article
- ARHGEF4-mediates the actin cytoskeleton reorganization of hepatic stellate cells in 3-dimensional collagen matrices.Cell adhesion & migration · 2019Article
- Reconstruction and analysis of competitive endogenous RNA network reveals regulatory role of long non‑coding RNAs in hepatic fibrosis.Molecular medicine reports · 2019Article
- Intercellular Communication between Hepatic Cells in Liver Diseases.International journal of molecular sciences · 2019Review
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Hepatic fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Migration of the activated HSCs to the site of injury is one of the key characteristics during the wound healing process. We have previously demonstrated that 14 kDa phosphohistidine phosphatase (PHP14) is involved in migration and lamellipodia formation of HSCs. However, the role of PHP14 in liver fibrosis remains unknown. In this study, we first assessed PHP14 expression and distribution in liver fibrotic tissues using western blot, immunohistochemistry, and double immunofluorescence staining. Next, we investigated the role of PHP14 in liver fibrosis and, more specifically, the migration of HSCs by Transwell assay and 3D collagen matrices assay. Finally, we explored the possible molecular mechanisms of the effects of PHP14 on these processes. Our results show that the PHP14 expression is up-regulated in fibrotic liver and mainly in HSCs. Importantly, TGF-β1 can induce PHP14 expression in HSCs accompanied with the activation of HSCs. Consistent with the previous study, PHP14 promotes HSCs migration, especially, promotes 3D floating collagen matrices contraction but inhibits stressed-released matrices contraction. Mechanistically, the PI3Kγ/AKT/Rac1 pathway is involved in migration regulated by PHP14. Moreover, PHP14 specifically mediates the TGF-β1 signaling to PI3Kγ/AKT pathway and regulates HSC migration, and thus participates in liver fibrosis. Our study identified the role of PHP14 in liver fibrosis, particularly HSC migration, and suggested a novel mediator of transducting TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway. KEY MESSAGES: PHP14 is up-regulated in fibrotic liver and activated hepatic stellate cells. The expression of PHP14 is induced by TGF-β1. The migration of hepatic stellate cells is regulated by PHP14. PHP14 is a mediator of TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway in hepatic stellate cells.
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