Session Time: 3:15pm-4:45pm
Presentation Time: 4:03pm-4:15pm
*Purpose: During chronic pancreatitis (CP), the extracellular matrix (ECM) of the pancreas is destroyed by a vicious cycle of parenchymal autodigestion by digestive exocrine enzymes and ensuing fibrosis. However, the islets persist until late stages of disease. We hypothesized that basal membrane laminins are produced to compensate for damage and repair processes to sustain islet cell function during CP. We examined expression ECM proteins in the pancreas of CP patients undergoing TPIAT and correlated with graft outcome.
*Methods: : Pancreatic sections from 29 CP patients undergoing TPIAT at our center were analyzed for extracellular matrix proteins (ECM) including P-laminin, laminin alpha 5, collagen VI, and perlecan and scored by positive staining area % to the whole tissue sections. Patient blood glucose and C-peptide levels were measured at 10-day and 3-month follow-up. Histological pancreatic sections from TPIAT patients from multiple etiological categories of CP to identify correlations with TPIAT outcomes.
*Results: Laminin alpha 5 (LAMA5) expression per area of pancreatic section was significantly higher in all CP patient etiological categories including alcoholic, hereditary, idiopathic, Oddi dysfunction and pancreatic divisum compared to healthy controls. Overall expression of LAMA5 correlated with ECM proteins P-laminin (R=0.63, p<0.001), collagen IV (R=0.67, p<0.001), and Perlecan (R=0.71, p<0.001). Increased cellular expression of LAMA5 was observed within islet endothelial vascular tissue and peri-islet basal membrane. Increased LAMA5 expression in the pancreas correlated with poor islet function and glycemic control at 10-day and 3-month follow up.
*Conclusions: CP is associated with increased expression of LAMA5 throughout the pancreas and in the islet basal membrane. Increased endothelial expression of LAMA5 and ECM proteins is indicative of progressive damage to the pancreas and correlates with poor TPIAT outcome.
To cite this abstract in AMA style:Liu Y, Kumano K, Vasu S, Darden CM, Lawrence M, Naziruddin B. High Laminin Alpha 5 Expression is Observed in the Pancreas of Chronic Pancreatitis Patients and Correlates with Poor Autologous Islet Transplant Outcome [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/high-laminin-alpha-5-expression-is-observed-in-the-pancreas-of-chronic-pancreatitis-patients-and-correlates-with-poor-autologous-islet-transplant-outcome/. Accessed September 29, 2020.
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