ABSTRACT
AIM: To investigate the effect of mesothelin in the remodeling of the endocrine pancreas in neonatal rats. METHODS: Overexpression or downregulation of mesothelin expression in INS-1 cells was carried out to investigate the effect of mesothelin during cell proliferation and cell apoptosis in vitro. Adenovirus-mediated RNA interference was performed to block mesothelin in vivo to directly assess the role of mesothelin in the remodeling of the endocrine pancreas in neonatal rats. RESULTS: Exogenous overexpression of mesothelin promoted cell proliferation, cell colony formation and enhanced cell resistance to apoptosis of INS-1 cells. Down-regulation of mesothelin made no difference in cell proliferation and apoptosis compared with that in the control group. After an injection of adenovirus-mesothelin, a significantly increased number of small islets appeared, and the expression of PCNA was decreased on day 7 and day 14 compared with the Ad-EGFP group. CONCLUSION: Mesothelin was able to promote ß cell proliferation in the remodeling stage of neonatal rats. Mesothelin may have an important role in the remodeling of the endocrine pancreas in neonatal rats.
Subject(s)
Cell Proliferation , GPI-Linked Proteins/metabolism , Insulin-Secreting Cells/metabolism , Islets of Langerhans/metabolism , Animals , Animals, Newborn , Apoptosis , Cell Line, Tumor , Female , GPI-Linked Proteins/genetics , Gene Expression Regulation , Islets of Langerhans/growth & development , Mesothelin , Pregnancy , RNA Interference , Rats, Sprague-Dawley , Signal Transduction , Time Factors , TransfectionABSTRACT
AIM: To investigate the mechanism behind ß-cell regeneration in neonatal rat pancreas treated with streptozotocin (STZ). METHODS: Neonatal Sprague Dawley rats were intraperitoneally injected with 70 mg/kg STZ. Body weight, pancreas weight and blood glucose were recorded every two days after the treatment. To identify the expression and location of transcription factors in the rat pancreas, double immunofluorescent staining was performed using antibodies to specific cell markers and transcription factors. RESULTS: Expression of Neurogenin 3 (Ngn3), a marker for endocrine precursor cells, was observed by immunofluorescence in a few ß-cells and many α-cells. The expression reached a peak 12 d after treatment. Pax4, a transcription factor that lies downstream of Ngn3 and plays an important role in ß-cell differentiation, was also expressed in the α-cells of STZ-treated rats. We did not observe significant changes in Nkx6.1, which is essential for ß-cell maturation in the treated rats. CONCLUSION: α-cells dedifferentiated into endocrine precursor cells and acquired the ability to dedifferentiate in the neonatal rat pancreas after STZ treatment.
