Short-reactivation of neurogenin-3 and mesenchymal microenvironment is require for β-cells differentiation during fetal pancreas development and islet regeneration

Rom J Morphol Embryol. 2014;55(2):305-11.

Abstract

Purpose: To investigate influencing factors of β-cells differentiation and microenvironment in embryonic development and regeneration, in order to conduct therapeutic efforts to broaden β-cells mass in diabetes.

Materials and methods: The expression of Ngn3 (Neurogenin-3) and microenvironment of β-cells differentiation during embryonic pancreas development at 4-12 weeks of gestation and regeneration after pancreatic islet injure observed by immunohistochemical staining.

Results: The results showed that the expression of Ngn3 not only in pancreas development but also in β-cells regeneration in rat diabetic model (DM) by streptozotocin (STZ) treatment. Pancreatic mesenchymal tissue always accompanied by islet cells differentiation and there is a short expression of Ngn3 occurrence before all islet cell types differentiated from pancreatic epithelium. The expression of Ngn3 including ectopic expression also appearance in β-cells injured rat pancreas. In addition, there are some Nestin-positive cells where located in pancreatic duct, islets and mesenchyme were detected in DM. Double immunostaining witness Brdu/Ngn3-positive cells was only in pancreatic mesenchyme after β-cells injure.

Conclusions: Our data demonstrated the expression of transcription factor Ngn3 and pancreatic mesenchymal microenvironment are important and necessary to promote pancreatic progenitors differentiated to islet cells regardless of pancreatic development or islets regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Differentiation
  • Embryo, Mammalian
  • Fetus / embryology
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Insulin-Secreting Cells / physiology*
  • Islets of Langerhans / physiology
  • Male
  • Mesenchymal Stem Cells / physiology
  • Nerve Tissue Proteins / metabolism*
  • Pancreas* / embryology
  • Pancreas* / metabolism
  • Pancreas* / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration*
  • Stem Cell Niche / physiology*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • NEUROG3 protein, human
  • Nerve Tissue Proteins