Abstract
Aim. To study genes regulating the extracellular matrix (ECM) and investigate the tissue remodelling following liver resection in porcine. Methods. Four pigs with 60% partial hepatectomy- (PHx-) induced liver regeneration were studied over six weeks. Four pigs underwent sham surgery and another four pigs were used as controls of the normal liver growth. Liver biopsies were taken upon laparotomy, after three and six weeks. Gene expression profiles were obtained using porcine-specific oligonucleotide microarrays. Immunohistochemical staining was performed and a proliferative index was assessed. Results. More differentially expressed genes were associated with the regulation of ECM in the resection group compared to the sham and control groups. Secreted protein acidic and rich in cysteine (SPARC) and collagen 1, alpha 2 (COL1A2) were both upregulated in the early phase of liver regeneration, validated by immunopositive cells during the remodelling phase of liver regeneration. A broadened connective tissue was demonstrated by Masson's Trichrome staining, and an immunohistochemical staining against pan-Cytokeratin (pan-CK) demonstrated a distinct pattern of migrating cells, followed by proliferating cell nuclear antigen (PCNA) positive nuclei. Conclusions. The present study demonstrates both a distinct pattern of PCNA positive nuclei and a deposition of ECM proteins in the remodelling phase of liver regeneration.
Highlights
The liver is known for its unique capacity to regenerate, with multiple studies having been conducted to assess the genetic mechanisms controlling the early phases of liver regeneration, as well as the corresponding histological changes.Significant changes in liver architecture during regeneration have been described such as the differential expression of cell-adhesion proteins, basement-membrane proteins, and changes in both intra- and intercellular junctions
Four pigs with 60% partial hepatectomy- (PHx-) induced liver regeneration were studied over six weeks
More differentially expressed genes were associated with the regulation of extracellular matrix (ECM) in the resection group compared to the sham and control groups
Summary
The liver is known for its unique capacity to regenerate, with multiple studies having been conducted to assess the genetic mechanisms controlling the early phases of liver regeneration, as well as the corresponding histological changes.Significant changes in liver architecture during regeneration have been described such as the differential expression of cell-adhesion proteins, basement-membrane proteins, and changes in both intra- and intercellular junctions. Hepatocytes are known to be self-renewing under normal conditions, the origin of hepatocytes under liver regeneration still remains controversial [12]. Previous studies have suggested the “streaming liver hypothesis,” implying that new hepatocytes arise in the periportal area and gradually migrate towards the pericentral area [12, 15]. Since this hypothesis remains controversial and has mainly been studied in rodents, we found it interesting to study
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