ArticleGut2016
Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches.
Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Monocyte Activation Drives Atrial Fibrillation in Hypertension.Cardiovascular drugs and therapy · 2026Article
- Diminished pleiotrophin as a new clue to pre-eclampsia: Linking impaired angiogenesis to adverse outcomes.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Article
- Pulmonary fibroblast subsets demonstrate differentially enriched signaling pathways during fibrosis resolution and repair.JCI insight · 2026Article
- Single-cell insights into hepatic fibroblasts and stellate cells: heterogeneity in matrix remodelling in development, health, and disease.Npj gut and liver · 2026Review
- Single-cell sequencing systematically analyzed the mechanism of Emdogain on the restoration of delayed replantation periodontal membrane.International journal of oral science · 2025Article
- Biliary fibrosis is an important but neglected pathological feature in hepatobiliary disorders: from molecular mechanisms to clinical implications.Medical review (2021) · 2024Review
- Rational engineering of lung alveolar epithelium.NPJ Regenerative medicine · 2023Article
- Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice.Cellular & molecular biology letters · 2023Article
- Pleiotrophin and metabolic disorders: insights into its role in metabolism.Frontiers in endocrinology · 2023Review
- Role of the Hippo pathway in liver regeneration and repair: recent advances.Inflammation and regeneration · 2022Review
- Understanding the cellular interactome of non-alcoholic fatty liver disease.JHEP reports : innovation in hepatology · 2022Review
- Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective heart morphogenesis in mice and zebrafish.American journal of physiology. Heart and circulatory physiology · 2022Article
- Deletion of pleiotrophin impairs glucose tolerance and liver metabolism in pregnant mice: Moonlighting role of glycerol kinase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Role of High-Mobility Group Box-1 in Liver Pathogenesis.International journal of molecular sciences · 2019Review
- Article
- Single-Cell RNA Sequencing of Human Embryonic Stem Cell Differentiation Delineates Adverse Effects of Nicotine on Embryonic Development.Stem cell reports · 2019Article
- The Expression, Functions, Interactions and Prognostic Values of PTPRZ1: A Review and Bioinformatic Analysis.Journal of Cancer · 2019Review
- Distinct Bone Marrow Sources of Pleiotrophin Control Hematopoietic Stem Cell Maintenance and Regeneration.Cell stem cell · 2018Article
- Hedgehog-YAP Signaling Pathway Regulates Glutaminolysis to Control Activation of Hepatic Stellate Cells.Gastroenterology · 2018Article
- Calcium Signaling in Liver Injury and Regeneration.Frontiers in medicine · 2018Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThe ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell niches produce pleiotrophin (PTN) to inactivate the PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby augmenting phosphoprotein-dependent signalling. We hypothesised that the DR is regulated by PTN/PTPRZ1 signalling.
designPTN-GFP, PTN-knockout (KO), PTPRZ1-KO, and wild type (WT) mice were examined before and after bile duct ligation (BDL) for PTN, PTPRZ1 and the DR. RDC and HSC from WT, PTN-KO, and PTPRZ1-KO mice were also treated with PTN to determine effects on downstream signaling phosphoproteins, gene expression, growth, and migration. Liver biopsies from patients with DRs were also interrogated.
resultsAlthough quiescent HSC and RDC lines expressed PTN and PTPRZ1 mRNAs, neither PTN nor PTPRZ1 protein was demonstrated in healthy liver. BDL induced PTN in MF-HSC and increased PTPRZ1 in MF-HSC and RDC. In WT mice, BDL triggered a DR characterised by periportal accumulation of collagen, RDC and MF-HSC. All aspects of this DR were increased in PTN-KO mice and suppressed in PTPRZ1-KO mice. In vitro studies revealed PTN-dependent accumulation of phosphoproteins that control cell-cell adhesion and migration, with resultant inhibition of cell migration. PTPRZ1-positive cells were prominent in the DRs of patients with ductal plate defects and adult cholestatic diseases.
conclusionsPTN, and its receptor, PTPRZ1, regulate the DR to liver injury by controlling the migration of resident cells in adult liver progenitor niches.
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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.