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Translocation of Porphyromonas gingivalis and Associated Islet Alterations in Mice and Human Pancreas

thesis
posted on 06.08.2019 by Haider Aljewari
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

History

Advisor

Watanabe, Keiko

Chair

Watanabe, Keiko

Department

Periodontics

Degree Grantor

University of Illinois at Chicago

Degree Level

Masters

Committee Member

Ilievski, Vladimir Olson, Steve Wicksteed, Barton

Submitted date

May 2019

Issue date

03/04/2019

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