[SPINK3: A novel growth factor that promotes rat liver regeneration]

Mol Biol (Mosk). 2016 May-Jun;50(3):457-65. doi: 10.7868/S0026898416030058.
[Article in Russian]


Serine peptidase inhibitor, Kazal type 3 (SPINK3) is a trypsin inhibitor, and also a growth factor that has an identical structure to epidermal growth factor (EGF), which could combine with epidermal growth factor receptor (EGFR) to promote cell proliferation. To shed light on the role and regulation mechanism of SPINK3 in rat liver regeneration (LR), Rat Genome 230 2.0 assay was used to detect the expression profiles of LR genes after partial hepatectomy (PH). The results showed that Spink3 was significantly up-regulated at 2-24 h and 72-168 h after PH. In the present study, RT-PCR and immunoblotting were used to validate the assay results. Ingenuity Pathway Analysis 9.0 (IPA) software was used to build the SPINK3 signaling regulating LR and analyze the possible mechanism. And then the expression of cell proliferation-associated gene Ccna2 was examined by RT-PCR in normal rat liver cell line BRL-3A in which Spink3 was overexpressed. The results showed that Ccna2 was significantly up-regulated in BRL-3A in which Spink3 was over-expressed. SPINK3 combining with EGFR accelerated cell proliferation during rat liver regeneration via P38, PKC, JAK-STAT and AKT pathways. Thus, SPINK3 was likely to promote hepatocytes proliferation in LR through P38, PKC, JAK-STAT and AKT.

Keywords: Kazal type 3 (SPINK3); cell proliferation; liver regeneration; serine peptidase inhibitor; signaling pathway.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Proliferation / genetics
  • Cyclin A2 / genetics*
  • Cyclin A2 / metabolism
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Hepatectomy*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Janus Kinases / genetics
  • Janus Kinases / metabolism
  • Liver / metabolism
  • Liver / surgery
  • Liver Regeneration / genetics*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Serine Proteinase Inhibitors / genetics*
  • Serine Proteinase Inhibitors / metabolism
  • Signal Transduction
  • Trypsin Inhibitor, Kazal Pancreatic
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Carrier Proteins
  • Ccna2 protein, rat
  • Cyclin A2
  • STAT Transcription Factors
  • Serine Proteinase Inhibitors
  • Spink1 protein, rat
  • Trypsin Inhibitor, Kazal Pancreatic
  • Egfr protein, rat
  • ErbB Receptors
  • Janus Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • p38 Mitogen-Activated Protein Kinases