RESUMO
AIMS/HYPOTHESIS: Islet Schwann (glial) cells and pericytes are the microorgan's accessory cells positioned at the external and internal boundaries facing the exocrine pancreas and endothelium, respectively, adjacent to the endocrine cells. Plasticity of glial cells and pericytes is shown in the glial scar formation after injury to the central nervous system. It remains unclear whether similar reactive cellular responses occur in insulitis. We applied three-dimensional (3D) histology to perform qualitative and quantitative analyses of the islet Schwann cell network and pericytes in normal, streptozotocin-injected (positive control of gliosis) and NOD mouse models. METHODS: Vessel painting paired with immunostaining of mouse pancreatic tissue was used to reveal the islet Schwann cells and pericytes and their association with vasculature. Transparent islet specimens were prepared by optical clearing to facilitate 3D confocal microscopy for panoramic visualisation of the tissue networks. RESULTS: In-depth microscopy showed that the islet Schwann cell network extends from the peri-islet domain into the core. One week after streptozotocin injection, we observed intra-islet perivascular gliosis and an increase in pericyte density. In early/moderate insulitis in the NOD mice, perilesional gliosis occurred at the front of the lymphocytic infiltration with atypical islet Schwann cell morphologies, including excessive branching and perivascular gliosis. Meanwhile, pericytes aggregated on the walls of the feeding arteriole at the peri- and intralesional domains with a marked increase in surface marker density. CONCLUSIONS/INTERPRETATION: The reactive cellular responses demonstrate plasticity and suggest a stop-gap mechanism consisting of the Schwann cells and pericytes in association with the islet lesion and vasculature when injury occurs.
Assuntos
Ilhotas Pancreáticas/efeitos dos fármacos , Pericitos/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pericitos/patologia , Células de Schwann/patologia , Estreptozocina/toxicidadeRESUMO
The ERG3 gene in Candida albicans was identified as a gene whose mRNA level was higher in the cph1/cph1 efg1/efg1 double mutant than in the wild-type cells. Further study showed that Efg1, but not Cph1, negatively regulated ERG3. Mutations in EFG1 consistently increased the susceptibility of the cells to antifungal agents.