Hepatocyte growth factor regulates proliferation and differentiation of epithelial monolayers derived from islets of postnatal rat pancreas
| Autor: | Rennian Wang, F Bacchus, N Yashpal, J Li |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Cell type Endocrinology Diabetes and Metabolism medicine.medical_treatment Fluorescent Antibody Technique Enteroendocrine cell Receptor tyrosine kinase Islets of Langerhans Endocrinology Internal medicine Insulin Secretion medicine Animals Insulin Rats Wistar Cells Cultured Cell Proliferation biology Hepatocyte Growth Factor Glucose transporter Cell Differentiation Epithelial Cells Stimulation Chemical Rats Animals Newborn biology.protein GLUT2 Hepatocyte growth factor Type I collagen medicine.drug |
| Zdroj: | Journal of Endocrinology. 183:163-171 |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1677/joe.1.05788 |
| Popis: | Hepatocyte growth factor (HGF) has been suggested to be a potent regulator of β-cell function and proliferation. The purpose of this study was to investigate whether HGF could regulate the proliferation and differentiation of islet-derived epithelial monolayers into insulin-producing cells. We have generated islet-derived epithelial monolayers that are enriched with cells expressing c-Kit, a tyrosine kinase receptor and putative marker, from isolated postnatal rat islets. Monolayers were cultured on type I collagen gel and treated in defined differentiation medium with or without HGF (50 ng/ml) for 7 days. Subsequently, the expression of transcription factors and pancreatic endocrine cell markers as well as c-Kit expression were compared between the HGF (HGF+), no HGF treatment (HGF−) and monolayers without differentiation medium (control) groups, using immunocytochemical and RT-PCR approaches. We observed that the number of c-Kit-, glucose transport type 2 (Glut2)- and the transcription factor pancreatic duodenal homeobox-1 (PDX-1)-expressing cells were significantly increased in the HGF+ group. The expression of insulin at the mRNA and protein level was also increased in this treatment group with a 1.7-fold increase in basal insulin release and a 2.3-fold increase in insulin content in comparison with the HGF− group. A high proliferative capacity was also found in the HGF+ group. Co-localization of insulin and PDX-1 or Glut2 was revealed frequently in cells treated with HGF+ with occasional co-staining of c-Kit and insulin observed. This study showed that HGF can activate the proliferation and differentiation of islet-derived epithelial monolayer into insulin-producing cells. However, no formation of islet-like clusters was observed. Taken together, this study implies that HGF mediates differentiation of immature cell types into insulin-expressing cells; however, HGF supplementation alone is insuffcient in restoring full β-cell function. |
| Databáze: | OpenAIRE |
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