ABSTRACT
Clinical evidence suggests that patients with chronic pancreatitis (CP) are prone to development of diabetes (chronic pancreatitis-related diabetes; CPRD), whereas the underlying mechanisms are not fully determined. Recently, we showed that the gradual loss of functional beta-cells in a mouse model for CPRD, partial pancreatic duct ligation (PDL), results from a transforming growth factor ß1 (TGFß1)-triggered beta-cell epithelial-mesenchymal transition (EMT), rather than from apoptotic beta-cell death. Here, the role of angiogenesis in CPRD-associated beta-cell EMT was addressed. We detected enhanced angiogenesis in the inflamed pancreas from CP patients by bioinformatic analysis and from PDL-mice. Inhibition of angiogenesis by specific antisera for vascular endothelial growth factor receptor 2 (VEGFR2), DC101, did not alter the loss of beta-cells and the fibrotic process in PDL-pancreas. However, DC101-mediated inhibition of angiogenesis abolished pancreatitis-induced beta-cell EMT and rendered it to apoptotic beta-cell death. Thus, our data suggest that angiogenesis promotes beta-cell survival in the inflamed pancreas, while suppression of angiogenesis turns beta-cell EMT into apoptotic beta-cell death. This finding could be informative during development of intervention therapies for CPRD.
Subject(s)
Diabetes Mellitus/genetics , Epithelial-Mesenchymal Transition/genetics , Insulin-Secreting Cells/metabolism , Neovascularization, Pathologic/genetics , Pancreatitis, Chronic/genetics , Animals , Antibodies, Monoclonal/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Diabetes Mellitus/etiology , Diabetes Mellitus/metabolism , Disease Models, Animal , Epithelial-Mesenchymal Transition/drug effects , Female , Gene Expression Profiling/methods , Humans , Insulin/metabolism , Insulin-Secreting Cells/drug effects , Male , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/prevention & control , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/metabolismABSTRACT
In this study, we de novo sequenced and analyzed the circular mitochondrial genome (mitogenome) of Tyrophagus putrescentiae. It was 14,156 bp long and contained a complete set of 37 genes, contrary to the initial published sequences; it included 22 tRNA sequences and the largest non-coding region. The mtDNA gene order of T. putrescentiae was found to be identical to that of Aleuroglyphus ovatus, Caloglyphus berlesei, and Rhizoglyphus robini (all Acaroidea). Most tRNAs of T. putrescentiae lack at least a D-arm or T-arm. Tyrophagus putrescentiae tRNAs also shared considerable structural and sequence similarity with the tRNAs of other reported Acaroidea species that have the full set of tRNAs. The largest non-coding region was located between trnF and trnS1, and it contained a microsatellite-like (AT)n sequence, short palindromic sequences, and several hairpin loops, as observed in other reported Acaroidea species (excepting Tyrophagus longior).
