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Translocation of Porphyromonas gingivalis and Associated Islet Alterations in Mice and Human Pancreas
thesisposted on 06.08.2019 by Haider Aljewari
In order to distinguish essays and pre-prints from academic theses, we have a separate category. These are often much longer text based documents than a paper.
Hypothesis: Chronic oral application of Porphyromonas gingivalis (Pg) results in translocation of Pg/gingipain to the pancreas and results in alteration of islet organization. Objective: 1) Determine if Pg/gingipain translocates to the pancreas in WTC57BL mice following chronic oral application of Pg, 2) Determine if Pg/gingipain is detected in the human post-mortem pancreas, 3) Determine expression of SerpinE1 and change in islet organization following chronic oral application of Pg. Methods: Paraffin embedded pancreata from control (N=10) and experimental mice (N=9) were sectioned for immunofluorescence and confocal microscopy to identify α- and β-cells and also localization of Pg/gingipain. Also, 3D and orthogonal analyses were performed to determine the localization of Pg/gingipain in mice pancreata. A total of 45 post-mortem human pancreata were selected to detect the presence of Pg/gingipain. qPCR was used to determine copy number of Pg genomic DNA in mice and human pancreata Results: The experimental group exhibited Pg/gingipain in islets as evidenced by immunofluorescence microscopy and qPCR confirming the translocation of orally applied Pg to the pancreas. Pg/gingipain was localized intranuclearly, perinuclearly and extracellularly in the experimental group but not in controls (p<0.001). Overall, 29% of human pancreata were positive for Pg/gingipain. The percentage of pancreas positive for Pg/gingipain was significantly higher in samples from diabetic patients compared to non-diabetic subjects (P< 0.01). Co-expression of uPA and SerpinE1 was identified in α-cells and not β-cells as well as islet cell reorganization occurred in the experimental and not the control group. Conclusions: Our results show that repeated oral application of Pg results in translocation of Pg/gingipain to pancreatic islets. SerpinE1 and uPA may mediate islet reorganization in the presence of Pg. Importantly, this is the first study showing the presence of Pg/gingipain in the non-cancerous human pancreata