title: Induction and contribution of beta platelet-derived growth factor signalling by hepatic stellate cells to liver regeneration after partial hepatectomy in mice.
abstract: Hepatic stellate cells (HSCs) activate during injury to orchestrate the liver's inflammatory and fibrogenic responses. A critical feature of HSC activation is the rapid induction of beta platelet-derived growth factor (β-PDGFR), which drives cellular fibrogenesis and proliferation; in contrast, normal liver has minimal β-PDGFR expression. While the role of β-PDGFR is well established in liver injury, its expression and contribution during liver regeneration are unknown. The aim of this study was to determine whether β-PDGFR is induced during liver regeneration following partial hepatectomy (pHx), and to define its contribution to the regenerative response.
  
  
  
  Control mice or animals with HSC-specific β-PDGFR-depletion underwent two-thirds pHx followed by assessment of hepatocyte proliferation and expression of β-PDGFR. RNA-sequencing from whole liver tissue of both groups after pHx was used to uncover pathways regulated by β-PDGFR signalling in HSCs.
  
  
  
  Beta platelet-derived growth factor expression on HSCs was up-regulated within 24 h following pHx in control mice, whereas absence of β-PDGFR blunted the expansion of HSCs. Mice lacking β-PDGFR displayed prolonged increases of transaminase levels within 72 h following pHx. Hepatocyte proliferation was impaired within the first 24 h based on Ki-67 and PCNA expression in β-PDGFR-deficient mice. This was associated with dysregulated growth in the β-PDGFR-deficient mice based on RNAseq with pathway analysis, and real-time quantitative PCR, which demonstrated reduced expression of Hgf, Igfbp1, Mapk and Il-6.
  
  
  
  Beta platelet-derived growth factor is induced in HSCs following surgical pHx and its deletion in HSCs leads to prolonged liver injury. However, there is no significant difference in liver regeneration.
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany.
authors.forename: Peri
authors.initials: P
authors.lastname: Kocabayoglu
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kojima
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hoshida
authors.affiliation: Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006498:Hepatectomy; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000254:growth & development* / Q000601:surgery; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; C577686:interleukin-6, mouse; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: liver regeneration; partial hepatectomy; pathway analysis; receptor tyrosine kinase